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Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures

Open AccessPublished:October 09, 2020DOI:https://doi.org/10.1194/jlr.S120001025
      A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.
      Lipids have become increasingly recognized as the central metabolites affecting human physiology and pathophysiology, and LIPID MAPS has recently expanded its tools, resources, data, and training as a free resource dedicated to serving the lipid research community (
      • O'Donnell V.B.
      • Dennis E.A.
      • Wakelam M.J.O.
      • Subramaniam S.
      LIPID MAPS: serving the next generation of lipid researchers with tools, resources, data, and training.
      ). Following development of the LIPID MAPS nomenclature, classification, and structural representation system (
      • Fahy E.
      • Subramaniam S.
      • Brown H.A.
      • Glass C.K.
      • Merrill Jr., A.H.
      • Murphy R.C.
      • Raetz C.R.
      • Russell D.W.
      • Seyama Y.
      • Shaw W.
      • et al.
      A comprehensive classification system for lipids.
      ,
      • Fahy E.
      • Subramaniam S.
      • Murphy R.C.
      • Nishijima M.
      • Raetz C.R.
      • Shimizu T.
      • Spener F.
      • van Meer G.
      • Wakelam M.J.
      • Dennis E.A.
      Update of the LIPID MAPS comprehensive classification system for lipids.
      ), an initial shorthand nomenclature was proposed (
      • Liebisch G.
      • Vizcaino J.A.
      • Köfeler H.
      • Trötzmüller M.
      • Griffiths W.J.
      • Schmitz G.
      • Spener F.
      • Wakelam M.J.
      Shorthand notation for lipid structures derived from mass spectrometry.
      ), which included a structural hierarchy as shown by others as well (
      • Ekroos K.
      From molecular lipidomics to validated clinical diagnosis.
      ,
      • Porta Siegel T.
      • Ekroos K.
      • Ellis S.R.
      Reshaping Lipid Biochemistry by Pushing Barriers in Structural Lipidomics.
      ). These were the first attempts to provide rules for reporting mass spectrometric data dependent on the power for structural resolution of lipids by the instrumental set-ups in use at that time.
      Today, we recognize that the field has evolved in often diverging ways and that this has not enabled a unifying naming convention to be adopted throughout. For example, alternative shorthand notation has evolved for some lipid classes, a plethora of newly determined structures for lipids from various classes and phylogenetic kingdoms (higher plants and yeasts) have been described, and progress in the technological development of mass spectrometers with greater structural resolution as well as advances in automation in interpreting high-throughput data has occurred. To address this, it is the aim of this report to take into account these developments and to present an update on the LIPID MAPS classification and a pragmatic highly usable shorthand notation for those active in lipid research. This update will focus on five of the eight LIPID MAPS categories (
      • Fahy E.
      • Subramaniam S.
      • Brown H.A.
      • Glass C.K.
      • Merrill Jr., A.H.
      • Murphy R.C.
      • Raetz C.R.
      • Russell D.W.
      • Seyama Y.
      • Shaw W.
      • et al.
      A comprehensive classification system for lipids.
      ), namely Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). Annotation is modified to permit annotation of oxygenated lipids and examples will be given for lipid classes occurring outside the mammalian kingdom.
      “Biological intelligence” has been considered as topical knowledge about a lipid molecule, such as its structural building blocks, enzymatic pathways for generation and metabolism, and biological functions (
      • Liebisch G.
      • Vizcaino J.A.
      • Köfeler H.
      • Trötzmüller M.
      • Griffiths W.J.
      • Schmitz G.
      • Spener F.
      • Wakelam M.J.
      Shorthand notation for lipid structures derived from mass spectrometry.
      ). Interpretation by biological evidence in shorthand notation can be useful when mass spectra contain structural ambiguities or lack of clear structural evidence. Consequently, annotations with the help of biological evidence contain assumptions, and it must be recognized and recorded that this may lead to misinterpretations. Moreover, in the pragmatic approach presented in this work, we will make more use of common and/or trivial names for the shorthand notation. For example, the structures of sterols, prostaglandins, resolvins, etc. have been characterized by chemical and spectroscopic methods, including stereochemistry, and common names exist, as do shorthand notations in many cases. Their mass spectra are also known; however, their stereochemistry and isomerism and other structural information often cannot be deduced directly from the spectra when these lipids are measured in biological samples. Assignment of a common name or of shorthand notation to such chromatographic and MS/MS data is permissible, but it may be based on annotation that includes biological intelligence, and that needs to be clearly stated as well.
      In any case, assumptions made should be striking a unique balance between what we think we know about structure and function of a lipid molecule and what a specific MS-based analytical method definitively informs us about the lipid structure.

      UPDATE ON NOMENCLATURE AND CLASSIFICATION

      Modification of Fatty Acyls by oxygen, either catalyzed enzymatically or by means of radical chemistry, is an important focus in biomedical research, due to the impressive biological activities of products thus obtained. Based on these two mechanisms, all compounds originating from polyunsaturated fatty acyls (PUFAs) having methylene-interrupted cis-double bonds (DBs) (also chemically referred to as allylic DBs) and being enzymatically or nonenzymatically oxygenated are grouped within the appropriate class in the Fatty Acyl category. Historically, the term “eicosanoid” has included “related oxygenated polyunsaturated fatty acids” with shorter or longer chain lengths, but in the LIPID MAPS classification, compounds are strictly assigned to a class based on their chain length (e.g., octadecanoids, eicosanoids, docosanoids). Recently, the common name “oxylipins”, standing for “oxygenated fatty acyls”, has come into widespread use. Similarly, in the Glycerophospholipids (GP) category, many newly described phospholipids contain oxygenated fatty acyls (or oxylipins) often termed “oxygenated phospholipids” (OxPLs). Those are produced by oxygenation of constituent fatty acyls enzymatically and nonenzymatically, or by chemical modification of polar head groups containing an amino function (PE and PS), i.e., N-modified phospholipids.
      In the following, we elaborate first on experimental prerequisites for correct annotation of lipid mass spectrometric data and, second, present the updates on rules for using shorthand notation. Finally, in order of categories, we present mostly in the form of easily readable tables, all updates on lipid nomenclature and classification including respective shorthand abbreviations according to the LIPID MAPS web resources and the updated shorthand notation for lipid species and lipid molecular species. To further enhance the understanding of shorthand notation, some chemical structures are presented in the tables. The updated shorthand notation schemes described herein have been incorporated into a number of key resources on the LIPID MAPS website, notably the LIPID MAPS Structure Database (LMSD) and the MS search tools (see the Hierarchical concept and application of shorthand notation section below), by generating level-specific abbreviations (e.g., sum-composition and chain-specific annotations) for lipid structures. This approach is important in terms of the development of MS search databases that are appropriate for the technique used (sum-composition databases for precursor ion data and chain-composition databases for MS/MS data).

      EXPERIMENTAL PREREQUISITES FOR CORRECT ANNOTATION

      All lipid species and lipid molecular species data presented need information on levels of structural resolution attained by mass spectrometric analysis, and sufficient supplementary data to justify annotation by shorthand notation. At minimum, such data should contain the measured intact m/z value, the adduct ion used for identification, the retention time when chromatography is applied, and the measured fragment m/z values.
      Assignment and therefore use of specific shorthand nomenclature for defined functional groups (TABLE 1A, TABLE 1B, TABLE 1C) requires additional techniques. An example is derivatization of hydroxyl groups by trimethylsilylation followed by GC/MS EI and analysis of fragment ions formed. In many cases ESI-MS/MS of underivatized constituent fatty acyls in general leads to specific product ions, if ESI populates a charge site near the functional group (
      • Murphy R.C.
      Tandem Mass Spectrometry of Lipids: Molecular Analysis of Complex Lipids.
      ). Definition of DB positions can be determined by several techniques including ozonolysis during analysis (OzID) (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or specific adduct formation with acetone in photochemical Paterno-Büchi reaction (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ). These reactions can be carried out in shotgun or LC-MS/MS experiments. High energy MS/MS has been used to assign DB position of fairly complex fatty acyls as well as methyl branching (
      • Cheng C.
      • Gross M.L.
      Applications and mechanisms of charge-remote fragmentation.
      ). Alternatively, GC/MS can be used including specific derivatization of the carboxylate group, to drive specific DB fragmentation in EI spectra (
      • Harvey D.J.
      Picolinyl esters for the structural determination of fatty acids by GC/MS.
      ). Chemical ionization techniques are also useful by application of specific chemical ionization reagent gases to define DB positions (
      • Michaud A.L.
      • Yurawecz M.P.
      • Delmonte P.
      • Corl B.A.
      • Bauman D.E.
      • Brenna J.T.
      Identification and characterization of conjugated fatty acid methyl esters of mixed double bond geometry by acetonitrile chemical ionization tandem mass spectrometry.
      ).
      TABLE 1AAbbreviations of functional groups/side chains
      Functional Group/Side ChainAbbreviation
      Ethyl branchEt
      Methyl branchMe
      BromoBr
      ChloroCl
      FluoroF
      IodoI
      NitroNO2
      EpoxyEp
      PeroxyOO
      MethoxyOMe
      Alkoxy (ether)oxy
      AminoNH2
      HydroperoxyOOH
      SulfanylSH
      hydroxyOH
      Oxo (keto/aldehyde; depending on position)oxo
      CyanoCN
      PhosphateP
      SulfateS
      Carboxylic acidCOOH
      GlycineG
      TaurineT
      The order of functional groups aligns with IUPAC hierarchy (
      • Wilkinson I.M.S.
      • IUPAC Commission on the Nomenclature of Organic Chemistry
      ).
      TABLE 1BAbbreviations of cyclic structures
      Cyclic StructuresAbbreviation
      Cyclopropylcy3
      Cyclopropenylcy3:1
      Cyclobutylcy4
      Cyclopentylcy5
      Cyclohexylcy6
      TABLE 1CAbbreviations of carbohydrate structures
      Carbohydrate StructuresAbbreviation
      HexoseHex
      GalactoseGal
      GlucoseGlc
      MannoseMan
      Neuraminic acidNeu
      N-acetyl hexosamineHexNAc
      N-acetyl galactosamineGalNAc
      N-acetyl glucosamineGlcNAc
      N-acetyl neuraminic acidNeuAc
      N-glycolylneuraminic acidNeuGc
      Keto-deoxy-glycero-galacto-nononic acidKdn
      Glucuronic acidGlcA
      XyloseXyl
      FucoseFuc
      Glycan annotation is based on IUPAC-approved abbreviations (https://www.ncbi.nlm.nih.gov/glycans/snfg.html) (
      • Neelamegham S.
      • Aoki-Kinoshita K.
      • Bolton E.
      • Frank M.
      • Lisacek F.
      • Lütteke T.
      • O'Boyle N.
      • Packer N.H.
      • Stanley P.
      • Toukach P.
      • et al.
      SNFG Discussion Group
      Updates to the symbol nomenclature for glycans guidelines.
      ).
      Common names of lipid species, e.g., for certain fatty acids and for oxygenated fatty acids denote a chemically defined structure including stereochemistry. For proper annotations in these cases, the analytical method has to provide for chiral separation of known stereoisomeric compounds. This validation demands data on reproducibility and limit of quantification. Similarly, when novel structures are described, analytical details proving structural details need to accompany the data. Guidelines for method validation and reporting of novel lipid molecules are currently being developed within the Lipidomics Standard Initiative (https://lipidomics-standards-initiative.org) as community-wide effort (
      • Liebisch G.
      • Ahrends R.
      • Arita M.
      • Arita M.
      • Bowden J.A.
      • Ejsing C.S.
      • Griffiths W.J.
      • Holcapek M.
      • Köfeler H.C.
      • Mitchell T.W.
      • et al.
      Lipidomics Standards Initiative Consortium
      Lipidomics needs more standardization.
      ).

      UPDATES ON GENERAL RULES FOR SHORTHAND NOTATION

      Here, we describe updates and rules applicable to all lipid categories described below. This includes rules on the hierarchical concept and application of the nomenclature and annotation of lipid structures as well as on annotation of stable isotope-labeled lipids. Three major updates are:
      • The term “DBs” is replaced by “double bond equivalents” (DBEs), because removal of two hydrogen atoms from precursor lipid forms a double bond, an oxo group or a cyclic structure. Frequently, MS does not distinguish between these alternatives.
      • Oxygen atoms represent not only the main component introduced during oxygenation, but occurs also in hydroxy groups as a principal structural feature in many lipid classes such as sphingoid bases. Because hydroxy, oxo or other oxygen functional groups may not be differentiated by high resolution/accurate mass analysis, annotation is done by the number of oxygens linked to the hydrocarbon chain.
      • Use of parentheses and brackets is minimized. Parentheses indicate primarily positions and, with regard to functional groups only those with numbers behind them, like (OH)2, (NO2), (NH2). The use of square brackets is restricted to chemical configurations R and S, to stable isotopes, and to the frame of carbons in a ring structure.

      Hierarchical concept and application of shorthand notation

      • Upon application of a validated MS-method, interpretation of mass spectra by “biological intelligence” and the use of common or trivial names, as alluded to specifically in the introduction, is permissible. Such annotations need to be clearly stated. Examples are ambiguities pertaining to bond type, oxygenated groups, and branched chains.
      • “Species level” is now the lowest hierarchical level. It represents the sum composition, i.e., sum of carbon atoms, DBEs, and number of additional oxygen atoms, e.g., FA 18:1;O. It thus replaces former “Lipid class level” mass (i.e., lipid class and the – uncharged - molecular mass). Of note, for sterols, the ABCD ring system is assumed and not expressed as DBE.
      • “Phosphate-position level” annotates positions of phosphate group(s), e.g., PIP(3′) or PIP2(4′,5′) at phosphatidylinositolphosphate.
      • “Molecular species level” pertains to all categories addressed here and is reached as soon as constituent fatty acyl/alkyl-residues are identified, e.g., TG 16:0_18:1_18:1, a triglyceride.
      • sn-position level” is a more refined level in GL and GP categories, enabling annotation of the sn-position of fatty acyl/alkyl constituents at the glycerol backbone as indicated by a slash, e.g., TG 16:0/18:1/18:1.
      • “DB-position level” or “DBE-position level” pertain to species having constituents with defined position of double bonds or double bond equivalents, e.g., FA 18:2 (9, 11);O.
      • “Structure defined level” annotates molecular species composed of various constituents and functional groups, yet without positions and stereochemical details, e.g., FA 18:2;OH.
      • “Full structure level” annotates molecular species composed of various constituents and functional groups including positions, yet without stereochemical details, e.g., FA 18:2(9Z,11E);13OH.
      • “Complete structure level” defines detailed structures of all functional groups including stereochemistry as shown in the LMSD, e.g., 13R-HODE, 13S-HODE (= common name).
      Figure 1 presents such a hierarchical scheme, taking the example of glucosylceramide.
      Figure thumbnail gr1
      Fig. 1Hierarchical scheme for the analysis of glucosylceramide. “Analysis” presents MS-data and “Annotation” the respective hierarchical levels with corresponding shorthand annotation. The chemical structure illustrates the Complete Structure level, numbers along the sphingoid base indicate conventional numbering of carbons therein.
      A word of caution is appropriate here: Annotations based solely on m/z features and on returns from database retrieval are frequently incorrect due to over-interpretation of experimental data, i.e., returns of chemically defined lipid molecules at Complete structure level. It is therefore of major importance that database search tools return appropriate annotations based on sum composition, i.e., at Species level and Molecular species level. Such tools are, for example, the LIPID MAPS MS search tools (https://lipidmaps.org/resources/tools/bulk_structure_searches_overview.php) (see also comment in the discussion) or the “ALEX lipid calculator” (http://alex123.info/ALEX123/MS.php).

      Annotation of lipid structures

      • Lipid species are annotated by class shorthand abbreviation (see Tables 2A-6A), followed by a space and C-atoms:DBE, e.g., TG 54:5, or C-atoms:DBE;O-atoms in fatty acyl/alkyl residues, e.g., FA 18:1;O or PC 38:3;O2.
        TABLE 2AClass abbreviations in Category FA
        Common NameLipid Class, LIPID MAPSAbbreviation
        Fatty acidsFatty acids and conjugates [FA01]FA
        Fatty alcoholsFatty alcohols [FA05]FOH
        Fatty aldehydesFatty aldehydes [FA06]FAL
        Acyl carnitinesFatty acyl carnitines [FA0707]CAR
        Acyl CoAsFatty acyl CoAs [FA0705]CoA
        N-acyl aminesN-acyl amines [FA0802]NA
        N-acyl ethanolaminesN-acyl ethanolamines (endocannabinoids) [FA0804]NAE
        N-acyl taurinesN-acyl amines [FA0802]NAT
        Wax estersWax monoesters [FA0701]WE
        Wax diestersWax diesters [FA0702]WD
        FA estolidesFAHFA wax monoesters [FA0701]FA-EST
      • Variable constituents like fatty acyls/alkyls are assigned based on their mass as number of C-atoms and number of DBE (C-atoms:DBE), when experimental proof for DB is provided the annotation is C-atoms:DB. Where applicable, the number of oxygen-atoms is added, separated by a semi-colon, e.g., C-atoms:DBE;O-atoms.
      • DB-position is indicated by a number according to D -nomenclature (geometry unknown) or a number followed by geometry (Z for cis, E for trans). Specific techniques are required for determination of DB-position (or geometry) to validly use this level of annotation, e.g., FA 18:2 (9, 12), FA 18:2(9Z,12Z).
      • Positions for all functional groups are stated in front of functional group abbreviation, e.g., FA 20:4;12OH.
      • Generally, all functional groups (see for abbreviations) are separated by a semicolon after the number of DBE. Functional groups are placed inside a separate pair of parentheses, only if more than one followed by the number of groups, e.g., FA 20:3;(OH)2;oxo. Moreover, functional groups containing numbers such as NO2 or NH2 are generally placed inside a separate pair of parentheses, e.g., FA 18:1;(NO2). The order of functional groups follows the IUPAC hierarchy (14).
      • Except for DBE/DB-position, proven positions of all other functional groups are stated according to D -nomenclature in front of the functional group abbreviation that are separated by a comma if more than one, e.g., FA 20:3(5Z,13E);11OH,15OH;9oxo
      • Cyclic structures cyX (X = number of ring atoms, see for abbreviations) are presented in front of other functional groups. Their structural details are annotated within a pair of square brackets. Within the square brackets the positions of ring atoms, separated by hyphen, are placed in front of the cyX annotation. Other functional groups are placed after the ring structure of the cyX annotation, e.g., FA 20:2;[8-12cy5;11OH;9oxo];15OH = 8-iso-PGE2 or PGE2.
      • Carbohydrate structures (), e.g., in complex glycosphingolipids, are annotated as described for glycans (https://www.ncbi.nlm.nih.gov/glycans) (15). When the sequence of sugars components is known they are shown in this order separated by a hyphen, e.g., Gal-Glc-Cer 18:1;O2/16:0. In case the sequence is unknown the components (followed by their number if more than one) are shown in alphabetic order in front of the respective lipid backbone, e.g., Gal2GlcCer 18:1;O2/16:0.
      • Acyl-linkages (N- and/or O-) are annotated by FA C-atoms:DBE inside a separate pair of parentheses with proven position in front, e.g., Cer 18:1;O2/26:0;26O(FA 18:2).
      • Alkyl-linkages (N- and/or O-) are annotated by C-atoms:DBE inside a separate pair of parentheses with proven position in front, e.g., FA 18:1(12Z);9O(16:1) for an ether lipid.
      • When functional groups are part of lipid class abbreviation, e.g., PIP2 or SPBP, their proven positions are shown inside parentheses, separated by a comma if more than one, e.g., PIP2(4′,5′) 38:4 or SPBP (1) 18:1;O2.
      • Greek letters are transcribed to Latin letters as follows: α to a, β to b, γ to g, δ to d, ω to w.
      • Proven stereochemistry is shown after the respective functional group/side chain in square brackets [R] or [S], e.g., FA 20:4(6Z,8E,10E,14Z);5OH[S],12OH[R] = LTB4.

      Annotation of isotope-labeled lipids

      • Isotope-containing lipid structures are indicated in square brackets annotating the isotope, followed by the number of isotopic atoms, e.g., FA 18:1[13C5].• Multiple isotopes are separated by a comma, e.g., FA 18:1[13C5,D4].
      • When positions of isotopes are known, they are indicated in a separate pair of parentheses in front of the isotope number, e.g., FA 18:1[(14,15,16,17,18)13C5].
      • Isotopes in fatty acyls or alkyls and in sphingoid bases are indicated in square brackets after the number of DBE, e.g., PC 34:1[D9] or PC O-16:0_18:1[13C5] and in Cer 34:1;O2[13C3], respectively. Isotopes in head groups of these structures are indicated in square brackets after class shorthand abbreviation, e.g., PC[D9] 34:1, TG[13C3] 54:3, SM[D9] 34:1;O2.
      • When positions of isotopes in the lipid are not known, they are indicated in square brackets in front of class shorthand abbreviation, e.g., [D5]PC 34:1, [13C7]TG 54:3.

      FATTY ACYLS (FA)

      Fatty acyls

      Shorthand abbreviations for Fatty Acyl classes are stated in Table 2A.
      Table 2B shows that lowest resolution level is based on m/z values, i.e., annotation at Species level (low mass resolution MS, e.g., carboxylate anion and oxygen atoms from functional groups). In addition, it is assumed that only a straight-chain fatty acid with or without DBE(s) is present. High mass resolution with accurate mass measurements may identify additional elements such as oxygen atoms of functional groups. Thus, a limited amount of structural information is provided at this level of analysis following the rules alluded to in the Annotation of lipid structures section, i.e., Species level. Annotation at DB-position level requires techniques such as ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ) or GC-MS. The use of trivial or common names for even simple fatty acids implies that additional methods have been used to define the exact structure, such as a straight-chain, positions of DBs, or DB geometries. Chiral chromatography preceding MS/MS is required for respective stereochemistry. Because this is generally not routinely done, investigators should note in their reports when using a common name for a fatty acid that “The identity and stereochemistry of the fatty acid species reported using a common name (e.g., oleic acid, linolenic acid, arachidonic acid, etc.) is assumed based on biological intelligence”. This comment applies to simple as well as complex lipids that include fatty acids as part of the structure (e.g., glycerophospholipids, triacylglycerols, etc.). Examples for shorthand notation of fatty acids are presented in Table 2B.
      TABLE 2BLevel-dependent shorthand notation for examples of fatty acids
      SubclassSpecies Level
      Uncharged molecular mass measured by low resolution MS of corresponding m/z from carboxylate anion (electrospray ionization) or molecular ion species (radical cation by EI).
      ,
      Annotation based on the assumption of a straight-chain fatty acyl plus functional groups based on exact mass measurements using a high-resolution mass spectrometer of fatty acyl indicating ion.
      DB-Position Level
      Positions of DBs determined by independent techniques such as ozonolysis (8) or photochemical derivatization (9).
      Full Structure Level
      Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      Complete Structure Level (= Common Name)
      Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      Straight-chain FAFA 12:0Laurate
      FA 14:0Myristate
      FA 16:0Palmitate
      FA 16:1FA 16:1(
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      )
      FA 16:1(9Z)Palmitoleate
      FA 18:0Stearate
      FA 18:1FA 18:1(
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      )
      FA 18:1(9Z)Oleate
      FA 18:1FA 18:1(
      • Harvey D.J.
      Picolinyl esters for the structural determination of fatty acids by GC/MS.
      )
      FA 18:1(11E)trans-Vaccenate
      FA 18:2FA 18:2(
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ,
      • Michaud A.L.
      • Yurawecz M.P.
      • Delmonte P.
      • Corl B.A.
      • Bauman D.E.
      • Brenna J.T.
      Identification and characterization of conjugated fatty acid methyl esters of mixed double bond geometry by acetonitrile chemical ionization tandem mass spectrometry.
      )
      FA 18:2(9Z,12Z)Linoleate
      FA 18:3FA 18:3(
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ,
      • Michaud A.L.
      • Yurawecz M.P.
      • Delmonte P.
      • Corl B.A.
      • Bauman D.E.
      • Brenna J.T.
      Identification and characterization of conjugated fatty acid methyl esters of mixed double bond geometry by acetonitrile chemical ionization tandem mass spectrometry.
      ,
      • Neelamegham S.
      • Aoki-Kinoshita K.
      • Bolton E.
      • Frank M.
      • Lisacek F.
      • Lütteke T.
      • O'Boyle N.
      • Packer N.H.
      • Stanley P.
      • Toukach P.
      • et al.
      SNFG Discussion Group
      Updates to the symbol nomenclature for glycans guidelines.
      )
      FA 18:3(9Z,12Z,15Z)α-Linolenate
      FA 18:3FA 18:3(
      • Porta Siegel T.
      • Ekroos K.
      • Ellis S.R.
      Reshaping Lipid Biochemistry by Pushing Barriers in Structural Lipidomics.
      ,
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ,
      • Michaud A.L.
      • Yurawecz M.P.
      • Delmonte P.
      • Corl B.A.
      • Bauman D.E.
      • Brenna J.T.
      Identification and characterization of conjugated fatty acid methyl esters of mixed double bond geometry by acetonitrile chemical ionization tandem mass spectrometry.
      )
      FA 18:3(6Z,9Z,12Z)γ-Linolenate
      FA 18:4FA 18:4(
      • Porta Siegel T.
      • Ekroos K.
      • Ellis S.R.
      Reshaping Lipid Biochemistry by Pushing Barriers in Structural Lipidomics.
      ,
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ,
      • Michaud A.L.
      • Yurawecz M.P.
      • Delmonte P.
      • Corl B.A.
      • Bauman D.E.
      • Brenna J.T.
      Identification and characterization of conjugated fatty acid methyl esters of mixed double bond geometry by acetonitrile chemical ionization tandem mass spectrometry.
      ,
      • Neelamegham S.
      • Aoki-Kinoshita K.
      • Bolton E.
      • Frank M.
      • Lisacek F.
      • Lütteke T.
      • O'Boyle N.
      • Packer N.H.
      • Stanley P.
      • Toukach P.
      • et al.
      SNFG Discussion Group
      Updates to the symbol nomenclature for glycans guidelines.
      )
      FA 18:4(6Z,9Z,12Z,15Z)Stearidonate
      FA 20:0Arachidate
      FA 20:3FA 20:3(
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ,
      • Harvey D.J.
      Picolinyl esters for the structural determination of fatty acids by GC/MS.
      ,
      • Wilkinson I.M.S.
      • IUPAC Commission on the Nomenclature of Organic Chemistry
      )
      FA 20:3(8Z,11Z,14Z)dihomo-γ-Linolenate
      FA 20:3FA 20:3(
      • Harvey D.J.
      Picolinyl esters for the structural determination of fatty acids by GC/MS.
      ,
      • Wilkinson I.M.S.
      • IUPAC Commission on the Nomenclature of Organic Chemistry
      ,
      • Galano J.M.
      • Lee Y.Y.
      • Oger C.
      • Vigor C.
      • Vercauteren J.
      • Durand T.
      • Giera M.
      • Lee J.C.
      Isoprostanes, neuroprostanes and phytoprostanes: an overview of 25 years of research in chemistry and biology.
      )
      FA 20:3(11Z,14Z,17Z)
      FA 20:3FA 20:3(
      • Ekroos K.
      From molecular lipidomics to validated clinical diagnosis.
      ,
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ,
      • Harvey D.J.
      Picolinyl esters for the structural determination of fatty acids by GC/MS.
      )
      FA 20:3(5Z,8Z,11Z)Mead acid
      FA 20:4FA 20:4(
      • Ekroos K.
      From molecular lipidomics to validated clinical diagnosis.
      ,
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ,
      • Harvey D.J.
      Picolinyl esters for the structural determination of fatty acids by GC/MS.
      ,
      • Wilkinson I.M.S.
      • IUPAC Commission on the Nomenclature of Organic Chemistry
      )
      FA 20:4(5Z,8Z,11Z,14Z)Arachidonate
      FA 20:5FA 20:5(
      • Ekroos K.
      From molecular lipidomics to validated clinical diagnosis.
      ,
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ,
      • Harvey D.J.
      Picolinyl esters for the structural determination of fatty acids by GC/MS.
      ,
      • Wilkinson I.M.S.
      • IUPAC Commission on the Nomenclature of Organic Chemistry
      ,
      • Galano J.M.
      • Lee Y.Y.
      • Oger C.
      • Vigor C.
      • Vercauteren J.
      • Durand T.
      • Giera M.
      • Lee J.C.
      Isoprostanes, neuroprostanes and phytoprostanes: an overview of 25 years of research in chemistry and biology.
      )
      FA 20:5(5Z,8Z,11Z,14Z,17Z)Eicosapentaenoate
      FA 22:0Behenate
      FA 22:6FA 22:6(
      • Liebisch G.
      • Vizcaino J.A.
      • Köfeler H.
      • Trötzmüller M.
      • Griffiths W.J.
      • Schmitz G.
      • Spener F.
      • Wakelam M.J.
      Shorthand notation for lipid structures derived from mass spectrometry.
      ,
      • Murphy R.C.
      Tandem Mass Spectrometry of Lipids: Molecular Analysis of Complex Lipids.
      ,
      • Cheng C.
      • Gross M.L.
      Applications and mechanisms of charge-remote fragmentation.
      ,
      • Liebisch G.
      • Ahrends R.
      • Arita M.
      • Arita M.
      • Bowden J.A.
      • Ejsing C.S.
      • Griffiths W.J.
      • Holcapek M.
      • Köfeler H.C.
      • Mitchell T.W.
      • et al.
      Lipidomics Standards Initiative Consortium
      Lipidomics needs more standardization.
      ,
      • Serhan C.N.
      • Levy B.D.
      Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators.
      ,
      • Taber D.F.
      • Morrow J.D.
      • Roberts II., L.J.
      A nomenclature system for the isoprostanes.
      )
      FA 22:6(4Z,7Z,10Z,13Z,16Z,19Z)Docosahexaenoate
      FA 24:0Lignocerate
      FA 24:1FA 24:1(
      • Neelamegham S.
      • Aoki-Kinoshita K.
      • Bolton E.
      • Frank M.
      • Lisacek F.
      • Lütteke T.
      • O'Boyle N.
      • Packer N.H.
      • Stanley P.
      • Toukach P.
      • et al.
      SNFG Discussion Group
      Updates to the symbol nomenclature for glycans guidelines.
      )
      FA 24:1(15Z)Nervonate
      FA 32:5FA 32:5(
      • Wilkinson I.M.S.
      • IUPAC Commission on the Nomenclature of Organic Chemistry
      ,
      • Galano J.M.
      • Lee Y.Y.
      • Oger C.
      • Vigor C.
      • Vercauteren J.
      • Durand T.
      • Giera M.
      • Lee J.C.
      Isoprostanes, neuroprostanes and phytoprostanes: an overview of 25 years of research in chemistry and biology.
      ,
      • Rokach J.
      • Khanapure S.P.
      • Hwang S.W.
      • Adiyaman M.
      • Lawson J.A.
      • FitzGerald G.A.
      Nomenclature of isoprostanes: a proposal.
      ,
      • Smith W.L.
      • Borgeat P.
      • Hamberg M.
      • Roberts II, L.J.
      • Willis A.
      • Yamamoto S.
      • Ramwell P.W.
      • Rokach J.
      • Samuelsson B.
      • Corey E.J.
      • et al.
      Nomenclature.
      ,
      • O'Donnell V.B.
      • Aldrovandi M.
      • Murphy R.C.
      • Kronke G.
      Enzymatically oxidized phospholipids assume center stage as essential regulators of innate immunity and cell death.
      )
      FA 32:5(14Z,17Z,20Z,23Z,26Z)Dotriacontapentaenoic acid; FA 32:5(n-6)
      FA 34:5FA 34:5 (
      • Taber D.F.
      • Morrow J.D.
      • Roberts II., L.J.
      A nomenclature system for the isoprostanes.
      ,
      • Göbel C.
      • Feussner I.
      Methods for the analysis of oxylipins in plants.
      ,
      • Bochkov V.N.
      • Oskolkova O.V.
      • Birukov K.G.
      • Levonen A-L.
      • Binder C.J.
      • Stöckl J.
      Generation and biological activities of oxidized phospholipids.
      ,
      • Pruett S.T.
      • Bushnev A.
      • Hagedorn K.
      • Adiga M.
      • Haynes C.A.
      • Sullards M.C.
      • Liotta D.C.
      • Merrill Jr., A.H.
      Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols.
      ,
      • Hoffmann N.
      • Rein J.
      • Sachsenberg T.
      • Hartler J.
      • Haug K.
      • Mayer G.
      • Alka O.
      • Dayalan S.
      • Pearce J.T.M.
      • Rocca-Serra P.
      • et al.
      mzTab-M: A data standard for sharing quantitative results in mass spectrometry metabolomics.
      )
      FA 34:5(19Z,22Z,25Z,28Z,31Z)Tetratriacontapentaenoic acid; FA 34:5(n-3)
      FA 36:6FA 36:6(
      • Medina S.
      • Gil-Izquierdo A.
      • Durand T.
      • Ferreres F.
      • Dominguez-Perles R.
      Structural/functional matches and divergences of phytoprostanes and phytofurans with bioactive human oxylipins.
      ,
      • Jahn U.
      • Galano J.M.
      • Durand T.
      A cautionary note on the correct structure assignment of phytoprostanes and the emergence of a new prostane ring system.
      ,
      • Colombo S.
      • Domingues P.
      • Domingues M.R.
      Mass spectrometry strategies to unveil modified aminophospholipids of biological interest.
      ,
      • Bochkov V.
      • Gesslbauer B.
      • Mauerhofer C.
      • Philippova M.
      • Erne P.
      • Oskolkova O.V.
      Pleiotropic effects of oxidized phospholipids.
      ,
      • O'Donnell V.B.
      • Ekroos K.
      • Liebisch G.
      • Wakelam M.
      Lipidomics: current state of the art in a fast moving field.
      ,
      • Holčapek M.
      • Dvorakova H.
      • Lisa M.
      • Giron A.J.
      • Sandra P.
      • Cvacka J.
      Regioisomeric analysis of triacylglycerols using silver-ion liquid chromatography-atmospheric pressure chemical ionization mass spectrometry: comparison of five different mass analyzers.
      )
      FA 36:6(18Z,21Z,24Z,27Z,30Z,33Z)Hexatriacontahexaenoic acid; FA 36:6(n-3)
      Fatty acyl esterFA 19:0FA 18:0;1OMeMethyl stearate
      Methyl branchedFA 20:0FA 16:0;3Me,7Me,11Me,15MeFA 16:0;3Me,7Me[R],11Me[R],15Me (Phytanate)
      HydroxyFA 18:0;OFA 18:0;9OHFA 18:0;9OH[S]
      OxoFA 11:1;O
      Annotation based on the assumption of a straight-chain fatty acyl plus functional groups based on exact mass measurements using a high-resolution mass spectrometer of fatty acyl indicating ion.
      FA 11:0;9oxoFA 11:0;9oxo
      CyclopropaneFA 19:1FA 19:0;[11-13cy3:0]Lactobacillic acid
      CyclopropeneFA 19:2FA 19:0;[9-11cy3:1(
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      )]
      Sterculic acid
      CyclopenteneFA 18:3FA 18:1(6Z);[14-18cy5:1(
      • Neelamegham S.
      • Aoki-Kinoshita K.
      • Bolton E.
      • Frank M.
      • Lisacek F.
      • Lütteke T.
      • O'Boyle N.
      • Packer N.H.
      • Stanley P.
      • Toukach P.
      • et al.
      SNFG Discussion Group
      Updates to the symbol nomenclature for glycans guidelines.
      )]
      Gorlic acid
      a Uncharged molecular mass measured by low resolution MS of corresponding m/z from carboxylate anion (electrospray ionization) or molecular ion species (radical cation by EI).
      b Annotation based on the assumption of a straight-chain fatty acyl plus functional groups based on exact mass measurements using a high-resolution mass spectrometer of fatty acyl indicating ion.
      c Positions of DBs determined by independent techniques such as ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      d Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      e Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      Fatty acyl esters, i.e., wax esters (WEs), wax diesters (WDs), fatty acyl estolides (FAHFAs, FA-EST), as well as N-acyl amines (NAs) and N-acyl ethanolamines (NAEs) are shown in Table 2C.
      TABLE 2CLevel-dependent shorthand notation for examples of fatty aldehydes, esters, and amides
      SubclassSpecies LevelMolecular Species LevelDB-Position Level
      Positions of DBs determined by independent techniques such as ozonolysis (8) or photochemical derivatization (9).
      Full Structure Level
      Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      Complete Structure Level (= Common Name)
      Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      Fatty aldehydeFAL 9:1;OFAL 9:1;OFAL 9:1(2);OHFAL 9:1(2E);4OH4-Hydroxynonenal
      Wax ester
      In shorthand notation for wax monoesters (WE), wax diesters (WD), and fatty amides (NA, NAE), alcohol and amine moieties precede the fatty acyl moiety.
      WE 32:1WE 14:0/18:1WE 14:0/18:1(9)WE 14:0/18:1(9Z)WE 14:0/18:1(9Z)
      Alkyl acetates
      In shorthand notation for wax monoesters (WE), wax diesters (WD), and fatty amides (NA, NAE), alcohol and amine moieties precede the fatty acyl moiety.
      WE 20:3WE 18:3/2:0WE 18:3(9,12,15)/2:0WE 18:3(9Z,12Z,15Z)/2:0WE 18:3(9Z,12Z,15Z)/2:0
      Wax diester
      In shorthand notation for wax monoesters (WE), wax diesters (WD), and fatty amides (NA, NAE), alcohol and amine moieties precede the fatty acyl moiety.
      WD 42:0WD 22:0/FA 10:0_FA 10:0WD 22:0/FA 10:0_FA 10:0WD 22:0;2O(FA 10:0),3O(FA 10:0)WD 22:0;2O(FA 10:0[S]),3O(FA 10:0[R])
      N-acyl amines (NA)
      In shorthand notation for wax monoesters (WE), wax diesters (WD), and fatty amides (NA, NAE), alcohol and amine moieties precede the fatty acyl moiety.
      NA 24:4NA 4:0/20:4NA 4:0/20:4(5,8,11,14)NA 4:0/20:4(5Z,8Z,11Z,14Z)NA 4:0/20:4(5Z,8Z,11Z,14Z)
      N-acyl ethanolamines (NAE)
      In shorthand notation for wax monoesters (WE), wax diesters (WD), and fatty amides (NA, NAE), alcohol and amine moieties precede the fatty acyl moiety.
      NAE 18:2NAE 18:2NAE 18:2(9,12)NAE 18:2(9Z,12Z)NAE 18:2(9Z,12Z), anandamide 18:2(n-6)
      Fatty acyl estolides (FA-EST)FAHFA 36:1;OFAHFA 18:1/18:0;OFAHFA 18:1(9)/18:0;OFAHFA 18:1(9Z)/9O(FA 18:0)FAHFA 18:1(9Z)/9O(FA 18:0[R])
      a Positions of DBs determined by independent techniques such as ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      b Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      c Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      d In shorthand notation for wax monoesters (WE), wax diesters (WD), and fatty amides (NA, NAE), alcohol and amine moieties precede the fatty acyl moiety.

      Oxygenated fatty acyls

      Lipidomic studies of “oxygenated fatty acyls,” commonly referred to as “oxylipins” or “oxygenated PUFAs” in the literature, involves analysis of enzymatically and nonenzymatically generated lipids such as octadecanoids, eicosanoids, docosanoids, do- and tetratriacontanoids (TABLE 2D, TABLE 2E, TABLE 2F). Enzymatically generated isomers include prostaglandins, leukotrienes, and the various “specialized pro-resolving mediators,” i.e., lipoxins, protectins, maresins, and resolvin D/Es (Table 2F) (
      • Serhan C.N.
      • Levy B.D.
      Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators.
      ). Nonenzymatic oxygenation of polyunsaturated fatty acids leads to numerous cyclic structures with various stereochemistry, such as phytoprostanes, isoprostanes, neuroprostanes, and all families of furans. Some of these isoprostanoids were identified over 25 years ago, particularly those of mammalian origin (
      • Galano J.M.
      • Lee Y.Y.
      • Oger C.
      • Vigor C.
      • Vercauteren J.
      • Durand T.
      • Giera M.
      • Lee J.C.
      Isoprostanes, neuroprostanes and phytoprostanes: an overview of 25 years of research in chemistry and biology.
      ) and more recently also as components in foods of plant origin (
      • Medina S.
      • Gil-Izquierdo A.
      • Durand T.
      • Ferreres F.
      • Dominguez-Perles R.
      Structural/functional matches and divergences of phytoprostanes and phytofurans with bioactive human oxylipins.
      ). The nomenclature for isoprostanoids is based on Taber, Morrow, and Roberts (
      • Taber D.F.
      • Morrow J.D.
      • Roberts II., L.J.
      A nomenclature system for the isoprostanes.
      ) and Rokach et al. (
      • Rokach J.
      • Khanapure S.P.
      • Hwang S.W.
      • Adiyaman M.
      • Lawson J.A.
      • FitzGerald G.A.
      Nomenclature of isoprostanes: a proposal.
      ), an update appeared in 2010 (
      • Jahn U.
      • Galano J.M.
      • Durand T.
      A cautionary note on the correct structure assignment of phytoprostanes and the emergence of a new prostane ring system.
      ). Table 2G presents the precursor-product relationships for the classes of phytoprostanes, isoprostanes, and neuroprostanes, for which abbreviations PhytoP, IsoP, and NeuroP, respectively, have been proposed.
      TABLE 2DShorthand notations for acyclic oxylipins at appropriate levels of annotation in lipidomic studies
      Species Level
      Uncharged molecular mass measured by low resolution MS of corresponding m/z from carboxylate anion (electrospray ionization) or molecular ion species (radical cation by EI).
      ,
      Annotation based on the assumption of a straight-chain fatty acyl plus functional groups based on exact mass measurements using a high-resolution mass spectrometer of fatty acyl indicating ion.
      DB-Position Level
      Positions of DBs determined by independent techniques such as ozonolysis (8) or photochemical derivatization (9).
      Structure Defined LevelFull Structure Level
      Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      Complete Structure Level (= Common Name)
      Common shorthand accepted by IUPAC (23).
      ,
      Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      FA 18:2;OFA 18:2(9,11);OFA 18:2;OHFA 18:2(9Z,11E);13OH13R-HODE, 13S-HODE
      FA 20:4;OFA 20:4(6,8,11,14);OFA 20:4;OHFA 20:4(6E,8Z,11Z,14Z);5OH5R-HETE, 5S-HETE
      FA 20:4;OFA 20:4(5,8,10,14);OFA 20:4;OHFA 20:4(5Z,8Z,10E,14Z);12OH12R-HETE, 12S-HETE
      FA 20:4;OFA 20:4(5,8,11,13);OFA 20:4;OHFA 20:4 (5Z,8Z,11Z,13E);15OH15R-HETE, 15S-HETE
      FA 20:4;O2FA 20:4(6,8,10,14);O2FA 20:4;(OH)2FA 20:4(6Z,8E,10E,14Z);5OH,12OHLTB4 (5S,12R)
      FA 20:5;O3FA 20:5(6,8,11,14,16);O3FA 20:5;OOH;OHFA 20:5(6E,8Z,11Z,14Z,16E);5OOH;18OH5S-Hp-18S-HEPE
      FA 20:5;O3FA 20:5(6,8,10,14,16);O3FA 20:5;(OH)3FA 20:5(6Z,8E,10E,14Z,16E);5OH,12OH,18OHResolvin E1 (5S,12R,18R)
      FA 22:6;O3FA 22:6(4,8,10,12,14,19);O3FA 22:6;(OH)3FA 22:6(4Z,8E,10Z,12E,14E,19Z);7OH,16OH,17OHResolvin D2 (7S,16R,17S)
      FA 22:6;O2FA 22:6(4,8,10,12,16,19);O2FA 22:6;(OH)2FA 22:6(4Z,8E,10E,12E,16Z,19Z);7OH,14OHMaresin 1 (7R,14S)
      a Uncharged molecular mass measured by low resolution MS of corresponding m/z from carboxylate anion (electrospray ionization) or molecular ion species (radical cation by EI).
      b Annotation based on the assumption of a straight-chain fatty acyl plus functional groups based on exact mass measurements using a high-resolution mass spectrometer of fatty acyl indicating ion.
      c Positions of DBs determined by independent techniques such as ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      d Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      e Common shorthand accepted by IUPAC (
      • Smith W.L.
      • Borgeat P.
      • Hamberg M.
      • Roberts II, L.J.
      • Willis A.
      • Yamamoto S.
      • Ramwell P.W.
      • Rokach J.
      • Samuelsson B.
      • Corey E.J.
      • et al.
      Nomenclature.
      ).
      f Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      TABLE 2EShorthand notations for cyclic oxylipins at appropriate levels of annotation in lipidomic studies
      Species Level
      Uncharged molecular mass measured by low resolution MS of corresponding m/z from carboxylate anion (electrospray ionization) or molecular ion species (radical cation by EI).
      ,
      Annotation based on the assumption of a straight-chain fatty acyl plus functional groups based on exact mass measurements using a high-resolution mass spectrometer of fatty acyl indicating ion.
      Structure Defined LevelFull Structure Level
      Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      Complete Structure Level (= Common Name)
      Common shorthand accepted by IUPAC (23).
      ,
      Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      FA 20:4;O3FA 20:3;(OH)2;oxoFA 20:2(5Z,13E);[8-12cy5;11OH;9oxo];15OHPGE2
      FA 20:4;O3FA 20:3;(OH)2;oxoFA 20:2(5Z,13E);[8-12cy5;9OH;11oxo];15OHPGD2
      FA 20:3;O3FA 20:3;(OH)3FA 20:2(5Z,13E);[8-12cy5;9OH,11OH];15OHPGF
      FA 20:3;O3FA 20:2;(OH)2;oxoFA 20:1(13E);[8-12cy5;11OH;9oxo];15OH8-iso-PGE1
      FA 20:3;O4FA 20:2;(OH)3;oxoFA 20:1(13E);[8-12cy5;9OH,11OH];15OH;6oxo6-oxo-PGF
      FA 20:3;O4FA 20:3;(OH)3;oxyFA 20:2(5Z,13E);[8-13cy6;9OH,11OH);11oxy];15OHTXB2
      FA 22:5;O3FA 22:5;(OH)3FA 22:4(4Z,7Z,10Z,18E);[13-17cy5;14OH,16OH];20OH20-F4-NeuroP
      a Uncharged molecular mass measured by low resolution MS of corresponding m/z from carboxylate anion (electrospray ionization) or molecular ion species (radical cation by EI).
      b Annotation based on the assumption of a straight-chain fatty acyl plus functional groups based on exact mass measurements using a high-resolution mass spectrometer of fatty acyl indicating ion.
      c Shorthand notation applies only when exact location and nature of functional group(s) are determined by specific fragment ions obtained by derivatization and GC/MS or specific product ions in a MS/MS experiment.
      d Common shorthand accepted by IUPAC (
      • Smith W.L.
      • Borgeat P.
      • Hamberg M.
      • Roberts II, L.J.
      • Willis A.
      • Yamamoto S.
      • Ramwell P.W.
      • Rokach J.
      • Samuelsson B.
      • Corey E.J.
      • et al.
      Nomenclature.
      ).
      e Validated assay is required to employ trivial names that engages appropriate internal standard, proper assessment of signal-to-noise, and a chromatographic based separation of potential isomers (GC or HPLC).
      TABLE 2FParent polyunsaturated fatty acids and oxygenated product specialized pro-resolving mediators
      Fatty AcidProduct ClassComplete Structure Level (= Common Name)
      Arachidonic acid; AA(n-6)EicosanoidLipoxin A4, lipoxin B4
      Eicosapentaenoic acid; EPA(n-3)EicosanoidResolvin E1, E2, E3
      Docosahexaenoic acid; DHA(n-3)DocosanoidResolvin D1, D2, D3, D4, D5, D6
      Docosapentaenoic acid; DPA(n-3)DocosanoidResolvin T1, T2, T3, T4
      Docosahexaenoic acid; DHA(n-3)DocosanoidPCTR1, PCTR2, PCTR3, protectin D1/neuroprotectin D1
      Docosahexaenoic acid; DHA(n-3)DocosanoidMCTR1, 2, 3, maresins 1, 2
      Docosahexaenoic acid; DHA(n-3)DocosanoidProtectin DX
      Dotriacontahexaenoic acid; FA 32:6(n-3)DotriacontanoidElovanoid ELV-N32
      Tetratriacontahexaenoic acid; FA 34:6(n-3)TetratriacontanoidElovanoid ELV-N34
      TABLE 2GParent polyunsaturated fatty acids and oxygenated product isoprostanoids
      Fatty AcidProduct ClassComplete Structure Level (= Common Name)
      α-Linoleic acid; ALA(n-3)OctadecanoidF1-PhytoP
      γ-Linolenic acid; GLA(n-6)OctadecanoidF1-PhytoPGLA
      Arachidonic acid; AA(n-6)EicosanoidF2-IsoP
      Eicosapentaenoic acid; EPA(n-3)EicosanoidF3-IsoP
      Adrenic acid; AdA(n-6)DocosanoidF2-IsoPAdA
      Docosapentaenoic acid; DPA(n-6)DocosanoidF3-NeuroPDPA(n-6)
      Docosapentaenoic acid; DPA(n-3)DocosanoidF3-NeuroPDPA(n-3)
      Docosahexaenoic acid; DHA(n-3)DocosanoidF4-NeuroP
      FA 22:4(4Z,7Z,10Z,18E);[13-17cy5;14OH,16OH];20OH
      Standards for structural validation by MS-inspection of these oxygenated fatty acids are described by Galano et al. (
      • Galano J.M.
      • Lee Y.Y.
      • Oger C.
      • Vigor C.
      • Vercauteren J.
      • Durand T.
      • Giera M.
      • Lee J.C.
      Isoprostanes, neuroprostanes and phytoprostanes: an overview of 25 years of research in chemistry and biology.
      ) and are in agreement with those referred to for oxylipins (
      • Göbel C.
      • Feussner I.
      Methods for the analysis of oxylipins in plants.
      ). Specific shorthand nomenclature has been previously suggested and widely used for polyunsaturated oxygenated fatty acids (
      • Smith W.L.
      • Borgeat P.
      • Hamberg M.
      • Roberts II, L.J.
      • Willis A.
      • Yamamoto S.
      • Ramwell P.W.
      • Rokach J.
      • Samuelsson B.
      • Corey E.J.
      • et al.
      Nomenclature.
      ).
      The use of a common name (Table 2B, D, E) for fatty acyls or in reporting lipidomic studies also requires a high level of validation, typically with a representative biological sample using, for example, stable isotope dilution and chiral LC-MS/MS or capillary GC/MS with highly reproducible retention times for authentic standards. Otherwise, assumptions made on the basis of biological intelligence must be clearly stated.

      GLYCEROLIPIDS (GL)

      See Table 3A and B for class abbreviations and examples, respectively. Lipid class abbreviation followed by number of C-atoms:number of DBE, for oxygenated lipids C-atoms:DBE;O-atoms, are as described in the Annotation of lipid structures section.
      TABLE 3AClass abbreviations in Category GL
      Common NameLipid Class, LIPID MAPSAbbreviation
      Monoacyl/alkylglycerides (monoglycerides)Monoradylglycerols [GL01]MG
      Diacyl/alkylglycerides (diglycerides)Diradylglycerols [GL02]DG
      Triacyl/alkylglycerides (triglycerides)Triradylglycerols [GL03]TG
      EstolidesEstolides [GL0305]TG-EST
      SulfoquinovosylmonoacylglycerolsGlycosylmonoacylglycerols [GL0401]SQMG
      MonogalactosylmonoacylglycerolGlycosylmonoacylglycerols [GL0401]MGMG
      DigalactosylmonoacylglycerolGlycosylmonoacylglycerols [GL0401]DGMG
      SulfoquinovosyldiacylglycerolsGlycosyldiacylglycerols [GL0501]SQDG
      MonogalactosyldiacylglycerolGlycosyldiacylglycerols [GL0501]MGDG
      DigalactosyldiacylglycerolGlycosyldiacylglycerols [GL0501]DGDG
      TABLE 3BExamples for shorthand notation of glycerolipids
      Bond TypeSpecies Level
      Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      Molecular Species Level
      Annotation requires MS/MS and detection of FA chain-specific fragments.
      sn-Position Level
      -Positions determined by specific analysis like differential mobility spectrometry (32), LC separation of isomeric species using silver ions (33).
      Full Structure Level
      DB-positions determined by independent techniques such as ozonolysis (8) or photochemical derivatization (9).
      AcylMG 18:0MG 18:0MG 0:0/18:0/0:0
      AlkylMG O-18:0MG O-18:0MG 0:0/O-18:0/0:0
      DiacylDG 34:1DG 16:0_18:1DG 16:0/18:1/0:0DG 16:0/18:1(9Z)/0:0
      Acyl-alkylDG O-34:1DG O-16:0_18:1DG O-16:0/18:1/0:0DG O-16:0/18:1(9Z)/0:0
      DialkylDG dO-32:1DG O-16:0_O-16:1DG O-16:0/O-16:1/0:0DG O-16:0/O-16:1(9Z)/0:0
      DG 30:1
      Annotation using low-resolution MS including the assumption of acyl chains only.
      TriacylTG 52:2TG 16:0_18:1_18:1TG 16:0/18:1/18:1TG 16:0/18:1(9Z)/18:1(11Z)
      TG 16:0_36:2 (only one acyl chain identified)TG 16:0_18:1(sn-2)_18:1
      Only acyl-chain at sn-2-position is defined.
      Acyl-alkylTG O-52:2TG O-16:0_18:1_18:1TG O-16:0/18:1/18:1TG O-16:0/18:1(9Z)/18:1(11Z)
      TG 51:2
      Annotation using low-resolution MS including the assumption of acyl chains only.
      Acyl-dialkylTG dO-52:2TG O-18:1_O-16:0_18:1TG O-18:1/O-16:0/18:1TG O-18:1(9Z)/O-16:0/18:1(9Z)
      TG 50:2
      Annotation using low-resolution MS including the assumption of acyl chains only.
      TrialkylTG tO-52:2TG O-18:1_O-16:0_O-18:1TG O-18:1/O-16:0/O-18:1TG O-18:1(9Z)/O-16:0/O-18:1(9Z)
      TG 49:2
      Annotation using low-resolution MS including the assumption of acyl chains only.
      TG-EstolideTG 68:3;O2TG 18:1_18:1_32:1;O2TG 16:0;O(FA 16:0)/18:1/18:1TG 16:0;5O(FA 16:0)/18:1(9Z)/18:1(9Z)
      a Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      b Annotation requires MS/MS and detection of FA chain-specific fragments.
      csn -Positions determined by specific analysis like differential mobility spectrometry (
      • Šala M.
      • Lisa M.
      • Campbell J.L.
      • Holcapek M.
      Determination of triacylglycerol regioisomers using differential mobility spectrometry.
      ), LC separation of isomeric species using silver ions (
      • Holčapek M.
      • Dvorakova H.
      • Lisa M.
      • Giron A.J.
      • Sandra P.
      • Cvacka J.
      Regioisomeric analysis of triacylglycerols using silver-ion liquid chromatography-atmospheric pressure chemical ionization mass spectrometry: comparison of five different mass analyzers.
      ).
      d DB-positions determined by independent techniques such as ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      e Annotation using low-resolution MS including the assumption of acyl chains only.
      f Only acyl-chain at sn-2-position is defined.
      Glycerolipids with known fatty acyl/alkyl constituents (molecular species):
      • separator _: sn-position of acyl/alkyl constituents is not known. Constituents are presented in the order of increasing number of C-atoms, as are DB (DBE)-numbers for each C-atom number, e.g., TG 16:0_18:1_18:3.
      • separator /: sn-position of acyl/alkyl constituents is proven (order sn-1/sn-2/sn-3; no FA linked 0:0), e.g., TG 16:0/18:3/18:1.
      • When only one acyl chain of TG is known, it is presented in front of the sum of the remaining two acyl residues, e.g., TG 16:0_36:3.
      • When only one of the sn-positions is defined, this is indicated inside a pair of parentheses, e.g., TG 16:0_18:1(sn-2)_18:0.
      Other bond types than ester bonds are indicated as follows in front of the sum of C-atoms for acyl/alkyl constituents:
      • O = alkyl, e.g., TG O-52:3
      • P = proven O-alk-1-enyl-bond (acid-sensitive ether bond in “neutral plasmalogens” is not counted as a DB/DBE within the acyl-chain), e.g., TG P-52:3 or at higher resolution TG P-16:0/18:3/18:1.
      • More than one “non”-ester bond is indicated in front of the bond type as d for di, t for tri, and e for tetra.

      GLYCEROPHOSPHOLIPIDS (GP)

      See TABLE 4A, TABLE 4B, TABLE 4C for abbreviations and examples. Shorthand notation for phospholipid species contains abbreviation for phospholipid classes, followed by number of C-atoms:number of DBE, i.e., PS 36:4, for oxygenated lipids C-atoms:DBE;O-atoms, i.e., PS 36:3;O, as described in the Annotation of lipid structures section.
      TABLE 4AClass abbreviations in Category GP
      Common NameLipid Class, LIPID MAPSAbbreviation
      Bis[monoacylglycero]phosphatesMonoacylglycerophosphomonoradylglycerols [GP0410]BMP
      CardiolipinsGlycerophosphoglycerophosphoglycerols [GP12]CL
      Phosphatidic acidsGlycerophosphates [GP10]PA
      PhosphatidylcholinesGlycerophosphocholines [GP01]PC
      PhosphatidylethanolaminesGlycerophosphoethanolamines [GP02]PE
      PhosphatidylgylcerolsGlycerophosphoglycerols [GP04]PG
      PhosphatidylgylcerolphosphatesGlycerophosphoglycerophosphates [GP05]PGP
      PhosphatidylinositolsGlycerophosphoinositols [GP06]PI
      PhosphatidylserinesGlycerophosphoserines [GP03]PS
      LysophospholipidsPrefix L
      Phosphatidylinositol-mannosidePIM
      Subclasses phosphatidylinositol phosphates
       Phosphatidylinositol-monophosphatesGlycerophosphoinositol monophosphates [GP07]PIP
       Phosphatidylinositol-3-phosphatesGlycerophosphoinositol monophosphates [GP07]PIP(3′)
       Phosphatidylinositol-4-phosphatesGlycerophosphoinositol monophosphates [GP07]PIP(4′)
       Phosphatidylinositol-5-phosphatesGlycerophosphoinositol monophosphates [GP07]PIP(5′)
       Phosphatidylinositol-bisphosphatesGlycerophosphoinositol bisphosphates [GP08]PIP2
       Phosphatidylinositol-3,4-bisphosphatesGlycerophosphoinositol bisphosphates [GP08]PIP2(3′,4′)
       Phosphatidylinositol-3,5-bisphosphatesGlycerophosphoinositol bisphosphates [GP08]PIP2(3′,5′)
       Phosphatidylinositol-4,5-bisphosphatesGlycerophosphoinositol bisphosphates [GP08]PIP2(4′,5′)
       Phosphatidylinositol-trisphosphatesGlycerophosphoinositol trisphosphates [GP09]PIP3
      N-modified phospholipids
      N-alkyl PSPS-N(Alk)
      N-acyl PSPS-N(FA)
       Phosphatidylserine-carboxyalkylpyrrolesPS-CAP
       Phosphatidylserine-malondialdehydesPS-MDA
      N-alkyl PEPE-N(Alk)
      N-acyl PEPE-N(FA)
       Phosphatidylethanolamine-carboxyalkylpyrrolesPE-CAP
       Phosphatidylethanolamine-glucosidesPE-Glc
       Phosphatidylethanolamine-glucuronidesPE-GlcA
       Phosphatidylethanolamine-α-ketoglucosidePE-GlcK
       Phosphatidylethanolamine-carboxymethylatesPE-CM
       Phosphatidylethanolamine-carboxyethylatesPE-CE
       Phosphatidylethanolamine-formamidesPE-FA
       Phosphatidylethanolamine-carbamidesPE-CA
       Phosphatidyethanolamine- malondialdehydesPE-MDA
       Phosphatidylethanolamine-hydroxynonenalsPE-HNE
       Phosphatidylethanolamine-isolevuglandinsPE-isoLG
      TABLE 4BExamples for shorthand notation of phospho- and lysophospholipids containing ester and/or ether bonds
      Bond TypeSpecies Level
      Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      Molecular SPECIES Level
      Annotation requires MS/MS and detection of FA chain specific fragments.
      sn-Position Level
      sn-Positions determined by specific MS analysis like differential mobility spectrometry (34).
      Full Structure Level
      Positions of DBs determined by independent techniques such as ozonolysis (8) or photochemical derivatization (9).
      DiacylBMP 34:1BMP 16:0_18:1BMP 16:0/0:0/18:1/0:0 sn-2/sn-3/sn-2′/sn-3′BMP 16:0/0:0/18:1(9Z)/0:0 sn-2/sn-3/sn-2′/sn-3′
      TetraacylCL 72:7CL 18:1_18:2_18:2_18:2CL 18:1/18:2/18:2/18:2 sn-1/sn-2/sn-1′/sn-2′CL 18:1(9Z)/18:2(9Z,12Z)/18:2(9Z,12Z)18:2(9Z,12Z) sn-1/sn-2/sn-1′/sn-2′
      CL 18:1_54:6 (only one acyl chain identified)
      CL 36:3_36:4 (known DG fragments)
      Tetra-alkylCL eO-80:0CL O-20:0/O-20:0/O-20:0/O-20:0CL O-20:0/O-20:0/O-20:0/O-20:0CL O-16:0(3Me,7Me,11Me,15Me)/O-16:0(3Me,7Me,11Me,15Me)/O-16:0(3Me,7Me,11Me,15Me)/O-16:0(3Me,7Me,11Me,15Me)
      DiacylPC 34:1
      Annotation using low resolution MS, QQQ and +PIS m/z 184 requires the assumption of even numbered carbon chains only.
      PC 16:0_18:1PC 16:0/18:1PC 16:0/18:1(9Z)
      AlkylPC O-34:1
      Annotation using low resolution MS, QQQ and +PIS m/z 184 requires the assumption of even numbered carbon chains only.
      PC O-16:0_18:1PC O-16:0/18:1PC O-16:0/18:1(9Z)
      DialkylPC dO-34:1PC O-16:0_O-18:1PC O-16:0/O-18:1PC O-16:0/O-18:1(9Z)
      DiacylPE 34:1
      Annotation using low resolution MS, QQQ and +NL 141 requires the assumption of even numbered carbon chains only.
      PE 16:0_18:1PE 16:0/18:1PE 16:0/18:1(9Z)
      PlasmalogenPE O-34:2
      Annotation using low resolution MS, QQQ and +NL 141 requires the assumption of even numbered carbon chains only.
      PE P-16:0/18:1
      Identification of plasmalogens (alk-1-enyl bond) require specific MS analysis (35).
      PE P-16:0/18:1(9Z)
      TriacylLCL 54:5LCL 18:1_18:2_18:2LCL 18:1/18:2/18:2/0:0LCL 18:1(9Z)/18:2(9Z,12Z)/18:2(9Z,12Z)/0:0
      MonoacylLPC 16:0
      Annotation using low resolution MS, QQQ and +PIS m/z 184 requires the assumption of even numbered carbon chains only.
      LPC 16:0LPC 16:0/0:0LPC 16:0/0:0
      MonoalkylLPC O-16:0
      Annotation using low resolution MS, QQQ and +PIS m/z 184 requires the assumption of even numbered carbon chains only.
      LPC O-16:0LPC O-16:0/0:0LPC O-16:0/0:0
      a Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      b Annotation requires MS/MS and detection of FA chain specific fragments.
      c sn-Positions determined by specific MS analysis like differential mobility spectrometry (
      • Maccarone A.T.
      • Duldig J.
      • Mitchell T.W.
      • Blanksby S.J.
      • Duchoslav E.
      • Campbell J.L.
      Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry.
      ).
      d Positions of DBs determined by independent techniques such as ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      e Annotation using low resolution MS, QQQ and +PIS m/z 184 requires the assumption of even numbered carbon chains only.
      f Annotation using low resolution MS, QQQ and +NL 141 requires the assumption of even numbered carbon chains only.
      g Identification of plasmalogens (alk-1-enyl bond) require specific MS analysis (
      • Zemski Berry K.A.
      • Murphy R.C.
      Electrospray ionization tandem mass spectrometry of glycerophosphoethanolamine plasmalogen phospholipids.
      ).
      TABLE 4CExamples for shorthand notation of phosphatidylinositol phosphates
      Bond TypeSpecies LevelPhosphate Position LevelMolecular Species Levelsn-Position LevelFull Structure Level
      DiacylPIP 36:1PIP(3′) 36:1PIP(3′) 16:0_18:1PIP(3′) 16:0/18:1PIP(3′) 16:0/18:1(9Z)
      DiacylPIP2 38:4PIP2(4′,5′) 38:4PIP2(4′,5′) 18:0_20:4PIP2(4′,5′) 18:0/20:4PIP2(4′,5′) 18:0/20:4(4Z,8Z,11Z,14Z)

      Phospholipids (PLs) and Lysophospholipids (LPLs)

      Molecular species of phospholipids with known fatty acyl/alkyl constituents (Table 4B):
      • separator _: sn-position of acyl/alkyl constituents is not known. Order of constituent presentation as described for glycerolipids, e.g., PC 16:0_18:2.
      • separator /: sn-position of acyl/alkyl constituents is proven (sn-1/sn-2 or sn-2/sn-3); no constituent 0:0; e.g., PC 16:0/18:2.
      • For BMP and CL classes sn-position order will be sn-2/sn-3/sn-2′/sn-3′ and sn-1/sn-2/sn-1′/sn-2′, respectively.
      • When only one acyl chain or DG moieties of CL are known, sum of acyl residues are presented, e.g., CL 16:0_54:3 and CL 34:1_36:2, respectively.
      Lysophospholipid classes are abbreviated as stated in LIPID MAPS nomenclature (Table 4A). Molecular species with unknown sn-position are presented as, e.g., LPE 18:1, with known sn-position as LPE 18:1/0:0 (Table 4B).
      Other bond types than ester bonds are indicated as described for Glycerolipids, e.g., for an ether phospholipid PE O-18:0/18:2, for a “plasmalogen” PE P-18:0/20:4.

      Phosphatidylinositol phosphates (PIPs)

      It is described in the Annotation of lipid structures section, when functional groups are part of lipid class abbreviation, their proven positions are shown directly at the abbreviation's end inside parentheses, separated by a comma if more than one. A prominent example is PIP3(3′,4′,5′). Table 4C shows that “Phosphate position level” identifies phosphate position at inositol ring, i.e., PIP(3′) 38:4, otherwise it would be PIP 38:4. For ease of handling by databases, numbers of phosphates are not written in lower case.

      N-modified phospholipids and lysophospholipids

      The amino function in PSs and PEs, including their lysoforms, is prone to react with a variety of electrophiles as has been shown in recent years (
      • Colombo S.
      • Domingues P.
      • Domingues M.R.
      Mass spectrometry strategies to unveil modified aminophospholipids of biological interest.
      ). The products are generally termed N-mod PL and N-mod LPL in abbreviated form, common names and respective abbreviations are shown in Table 4A. Structures at Species-, Molecular species-, and sn-Position levels are presented in shorthand notation as described in the Annotation of lipid structures, Glycerolipids (GL), and Glycerophospholipids (GP) sections; specific examples are shown in Table 4D.
      TABLE 4DExamples for shorthand notation of N-modified phospholipids
      Oxidative ModificationSpecies Level
      Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      Molecular Species Level
      Annotation requires MS/MS and detection of FA chain specific fragments.
      sn-Position Level
      sn-Positions determined by specific MS analysis like differential mobility spectrometry (34).
      Full Structure Level
      N-alkylPS-N(Alk) 40:3PS-N(6:0)16:0_18:3PS-N(6:0) 16:0/18:3PS-N(6:0) 16:0/18:3(9Z,12Z,15Z)
      N-acylPE-N(FA) 54:5PE-N(FA 18:1) 16:0_20:4PE-N(FA 18:1) 16:0/20:4PE-N(FA 18:1(9Z)) 16:0/20:4(4Z,8Z,11Z,14Z)
      Hydroxynonenal adductPE-HNE 36:4PE-HNE 16:0_20:4PE-HNE 16:0/20:4PE-HNE 16:0/20:4(4Z,8Z,11Z,14Z)
      a Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      b Annotation requires MS/MS and detection of FA chain specific fragments.
      c sn-Positions determined by specific MS analysis like differential mobility spectrometry (
      • Maccarone A.T.
      • Duldig J.
      • Mitchell T.W.
      • Blanksby S.J.
      • Duchoslav E.
      • Campbell J.L.
      Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry.
      ).

      OxPLs

      Phospholipids containing PUFA-constituents having methylene-interrupted cis-DBs (allylic DBs) and/or polar headgroups having amino-residues are susceptible to oxidation with formation of OxPLs. OxPL, so far, is a general term for a class of lipids produced by several processes that most often cannot be distinguished by MS analysis of the products. In all these cases, the products are called OxPLs (
      • Bochkov V.N.
      • Oskolkova O.V.
      • Birukov K.G.
      • Levonen A-L.
      • Binder C.J.
      • Stöckl J.
      Generation and biological activities of oxidized phospholipids.
      ).
      Respective modes for production are the following:
      • Oxygenation of PL to produce OxPL by direct action of lipoxygenases on PUFA constituents of PL gives rise to enzymatically produced specific oxPL. The stereochemistry of the resulting PUFA component usually reflects the specificity of the specific enzyme involved (26).
      • The Land's cycle is an alternative mechanism for enzymatic OxPL formation. Free, unesterified PUFAs liberated by phospholipase A2 and other enzymatic pathways from PL are first oxygenated by lipoxygenases, cyclooxygenases or CYP450 oxygenases. The resulting oxygenated PUFAs can then be reesterified into PLs resulting in the indirect enzymatic formation of specific oxPL.
      • Nonenzymatic reactions are induced by free-radical oxygen/nitrogen species reacting directly with the PUFA constituents of PL or with free PUFAs which become incorporated into the PL by acyl transferases producing nonenzymatically derived oxPL. This oxygen transfer to PUFAs can further lead to DB rearrangement, cyclization and even truncation of such acyl-chains resulting in complex mixtures of oxPL (27).
      • Nonradical reactive oxygen species like singlet oxygen or ozone can also contribute to PL oxidation with generation of full-chain or fragmented oxPL.
      • PL having a polar head group with a modified amino-function (PE and PS) form a subclass named oxPL-Nmod.
      Shorthand notation for OxPLs in general are presented in Table 4E.
      Table 4EExamples for shorthand notation of OxPLs
      Oxidative ModificationSpecies Level
      Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      Molecular Species Level
      Annotation requires MS/MS and detection of FA chain specific fragments.
      sn-Position Level
      sn-Positions determined by specific MS analysis like differential mobility spectrometry (34).
      Structure Defined LevelFull Structure Level
      HydroxylationPC 36:4;OPC 16:0_20:4;OPC 16:0/20:4;OPC 16:0/20:4;OHPC 16:0/20:4(5Z,8Z,10E,14Z);12OH
      PC 34:1;O2PC 16:0_18:1;O2PC 16:0/18:1;O2PC 16:0/18:1;(OH)2PC 16:0/18:1(9Z);12OH,13OH
      EpoxidePC 34:2;OPC 16:0_18:2;OPC 16:0/18:2;OPC 16:0/18:1;EpPC 16:0/18:1(9Z);12Ep
      HydroperoxidePC 34:2;O2PC 16:0_18:2;O2PC 16:0/18:2;O2PC 16:0/18:2;OOHPC 16:0/18:2(9Z,11E);13OOH
      PeroxidePC 34:2;O2PC 16:0_18:2;O2PC 16:0/18:2;O2PC 16:0/18:1;OOPC 16:0/18:1(9Z);12OO
      AldehydePC 21:1;OPC 16:0_5:1;OPC 16:0/5:1;OPC 16:0/5:0;oxoPC 16:0/5:0;5oxo
      Carboxylic acidPC 25:1;O2PC 16:0_9:1;O2PC 16:0/9:1;O2PC 16:0/9:0;COOHPC 16:0/9:0;8COOH
      Hydroxy-aldehydePC 26:3;O2PC 18:1_8:2;O2PC 18:1/8:2;O2PC 18:1/8:1;OH;oxoPC 18:1(9Z)/8:1(6E);5OH;8oxo
      PC sn-2 positionPC 36:4;O3PC 16:0_20:4;O3PC 16:0/20:4;O3PC 16:0/20:2;[cy5;OH;oxo];OHPC 16:0/20:2(5Z,13E);[8-12cy5;11OH;9oxo];15OH (common name 8-IsoPGE2-PC)
      a Annotation based on exact mass measurements using a high-resolution mass spectrometer, which allows differentiation of isobaric acyl and alkyl species.
      b Annotation requires MS/MS and detection of FA chain specific fragments.
      c sn-Positions determined by specific MS analysis like differential mobility spectrometry (
      • Maccarone A.T.
      • Duldig J.
      • Mitchell T.W.
      • Blanksby S.J.
      • Duchoslav E.
      • Campbell J.L.
      Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry.
      ).

      SPHINGOLIPIDS (SP)

      Apart from sphingosine containing 18 C-atoms with two hydroxyl groups and one DB, other sphingoid bases reveal prominent backbones as well, particularly in brain or nonmammalian specimens (
      • Pruett S.T.
      • Bushnev A.
      • Hagedorn K.
      • Adiga M.
      • Haynes C.A.
      • Sullards M.C.
      • Liotta D.C.
      • Merrill Jr., A.H.
      Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols.
      ). Consequently, the abbreviation SPB is strongly recommended as shorthand notation for the general term “sphingoid bases,” Cer for ceramides, and SM for sphingomyelins (Table 5A). Table 5B, C, and D define, in addition, shorthand notation according to structural resolution of sphingolipids. The updated rules for shorthand notation are the following:
      • In case the long-chain base is not known, the sum composition of sphingoid base and fatty acid is shown as number of C-atoms:DBE;O-atoms, e.g., SPB 34:1;O2.
      • In ceramides the sphingoid backbone is annotated C-atoms:DBE;O-atoms separated by a slash from the number of C-atoms:DBE;O-atoms of the N-linked fatty acid, e.g., Cer 18:1;O2/16:0.
      • DB geometry and positions of hydroxyl groups (or other functional groups) are annotated as described for fatty-acyl-chains in Tab. 2B, e.g., Cer 18:1(4E);1OH,3OH/16:0.
      • When the number of hydroxyl groups cannot be determined, numbers of C-atoms and DBE are assigned under the assumption of the number of hydroxyl groups in the major sphingoid base for that organism (e.g., dihydroxy in mammals).
      • For further characterization of N-linked fatty acids, the rules as described in the Annotation of lipid structures section apply. The position of a fatty acid esterified to an N-linked hydroxy-fatty acyl is shown in a separate pair of parentheses xO(FA C-atoms:DBE) with x denoting the position of hydroxyl group (Δ nomenclature) in the N-linked fatty acids, e.g., Cer 18:1;O2/26:0;18O(FA 16:0).
      • Any modification linked to a sphingoid base-OH is written in front of the (sub)class abbreviation with the integrated position number in parenthesis at the end of abbreviation, e.g., FA 24:1-ACer (1) 18:1;3OH/16:0 for an acylceramide, Gal-Cer (1) 18:0;3OH/16:0 for a galactosylceramide.
      • Consequently, in shorthand notation from “Structure defined level” onwards only unmodified OH-groups of the sphingoid base are annotated.
      • Shorthand notation for carbohydrate moieties is stated in Table 1C and examples are shown in Table 5D.
      • For annotation of the sugar moiety in complex glycosphingolipids we refer to current practice in glycan science (https://www.ncbi.nlm.nih.gov/glycans) (15). When the sequence of sugars components is known, they are shown in this order separated by a hyphen. In case the sequence is unknown the components (followed by their number if more than one) are shown in alphabetic order in front of the respective lipid backbone. Annotation of the ceramide part follows the rules described above.
      • Sphingoid base phosphates with unknown phosphate position are represented by SPBP, e.g., SPBP 18:1;(OH)2.
      • Sphingoid base phosphates with known position of phosphate and of OH-positions is annotated by, e.g., SPBP (1) 18:1(4E);3OH.
      • Ceramide phosphates with unknown phosphate position are represented by CerP, e.g., CerP 18:1;O2/16:0.
      • Ceramide phosphates with known position of phosphate and of OH-positions are annotated by, e.g., CerP (1) 18:1(4E);3OH.
      • Ceramide phosphates with 1,3 cyclic phosphate and known OH-positions are annotated by, e.g., CerP (1, 3) 18:1(4E).
      TABLE 5AClass abbreviations in Category SP
      Common NameLipid Class, LIPID MAPSAbbreviation
      Sphingoid basesSphingoid bases [SP01]SPB
      Sphingoid base-phosphatesSphingoid bases [SP0105]SPBP
      CeramidesCeramides [SP02]Cer
      Ceramide-phosphatesCeramide phosphates [SP0205]CerP
      Acyl CeramidesAcylceramides [SP0204]ACer
      SphingomyelinsPhosphosphingolipids [SP03]SM
      HexosylceramidesNeutral glycosphingolipids [SP05]HexCer
      GlucosylceramideNeutral glycosphingolipids [SP05]GlcCer
      GalactosylceramideNeutral glycosphingolipids [SP05]GalCer
      DihexosylceramidesNeutral glycosphingolipids [SP05]Hex2Cer
      LactosylceramideNeutral glycosphingolipids [SP05]LacCer
      SulfatidesSulfoglycosphingolipids (sulfatides) [SP0602]SHexCer
      InositolphosphorylceramidesCeramide phosphoinositols [SP0303]IPC (PI-Cer)
      EthanolaminephosphorylceramidesCeramide phosphoethanolamines [SP0302]EPC (PE-Cer)
      GlycosylinositolphosphorylceramidesCeramide phosphoinositols [SP0303]GIPC
      Mannosyl-inositolphosphoceramidesCeramide phosphoinositols [SP0303]MIPC
      Mannosyl-diinositolphosphoceramideCeramide phosphoinositols [SP0303]M(IP)2C
      TABLE 5BExamples for shorthand notation of sphingolipids with a free amino group
      Sphingoid BaseSpecies Level
      Annotation based on exact mass measurements using a high-resolution mass spectrometer.
      Structure Defined LevelFull Structure Level
      Positions of functional groups and DBs determined by independent techniques such as chromatographic resolution, ozonolysis (8) or photochemical derivatization (9).
      SphingosineSPB 18:1;O2SPB 18:1;(OH)2SPB 18:1(4E);1OH,3OH
      3-Keto-sphinganineSPB 18:1;O2SPB 18:0;OH;oxoSPB 18:0;1OH;3oxo
      SphinganineSPB 18:0;O2SPB 18:0;(OH)2SPB 18:0;1OH,3OH
      SphingadieneSPB 18:2;O2SPB 18:2;(OH)2SPB 18:2(4E,14Z);1OH,3OH
      PhytosphingosineSPB 18:0;O3SPB 18:0;(OH)3SPB 18:0;1OH,3OH,4OH
      C20-sphingosineSPB 20:1;O2SPB 20:1;(OH)2SPB 20:1(4E);1OH,3OH
      Sphingosine-1-phosphateSPBP 18:1;O2SPBP 18:1;OHSPBP(1) 18:1(4E);3OH
      Sphinganine-1-phosphateSPBP 18:0;O2SPBP 18:0;OHSPBP(1) 18:0;3OH
      1-Deoxymethyl-sphinganineSPB 17:0;OSPB 17:0;OHSPB 17:0;2OH
      1-Deoxy-sphinganineSPB 18:0;OSPB 18:0;OHSPB 18:0;3OH
      LysoinositolphosphorylceramidesLIPC 18:0;O3LIPC 18:0;(OH)2LIPC(1) 18:0;3OH,4OH
      LysosphingomyelinLSM 18:1;O2LSM 18:1;OHLSM(1) 18:1(4E);3OH
      a Annotation based on exact mass measurements using a high-resolution mass spectrometer.
      b Positions of functional groups and DBs determined by independent techniques such as chromatographic resolution, ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      TABLE 5CExamples for shorthand notation of sphingolipids containing an amide bound fatty acid
      PhylaSpecies Level
      Annotation based on exact mass measurements using a high-resolution mass spectrometer.
      Molecular Species Level
      Annotation requires MS/MS enabling detection of sphingoid base and/or N-linked FA.
      Full Structure Level
      Positions of functional groups and DBs determined by independent techniques such as chromatographic resolution, ozonolysis (8) or photochemical derivatization (9).
      MammalianCer 34:1;O2Cer 18:1;O2/16:0Cer 18:1(4E);1OH,3OH/16:0
      MammalianCer 34:0;O2Cer 18:0;O2/16:0Cer 18:0;1OH,3OH/16:0
      MammalianACer 58:1;O2FA 24:1-ACer 18:1;O2/16:0FA 24:1-ACer(1) 18:1(4E);3OH/16:0
      MammalianCerP 34:1;O2CerP 18:1;O2/16:0CerP(1) 18:1(4E);3OH/16:0
      MammalianSM 36:2;O2
      Annotation using low resolution MS QQQ and a PIS m/z 184 requires the assumption of a sphingoid base with two hydroxyl groups.
      SM 18:2;O2/18:0SM(1) 18:2(4E,14Z);3OH/18:0
      MammalianSM 44:2;O2
      Annotation using low resolution MS QQQ and a PIS m/z 184 requires the assumption of a sphingoid base with two hydroxyl groups.
      SM 20:1;O2/24:1SM(1) 20:1(4E);3OH/24:1(15Z)
      MammalianCer 62:3;O4Cer 18:1;O2/26:0;O(FA 18:1)
      Annotation with structural characterization of O-acyl in N-linked acyl chain.
      Cer 18:1(4E);1OH,3OH/26:0;26O(FA 18:1(9Z))
      Cer 18:1;O2/44:2;O2
      Annotation without structural differentiation of N-linked acyl chain.
      PlantIPC 42:1;O4IPC 18:1;O3/24:0;OIPC(1) 18:1(8E);3OH,4OH/24:0;2OH
      YeastCer 44:0;O5Cer 18:0;3O/26:0;O2Cer 18:0;1OH,3OH,4OH/26:0;2OH,3OH
      a Annotation based on exact mass measurements using a high-resolution mass spectrometer.
      b Annotation requires MS/MS enabling detection of sphingoid base and/or N-linked FA.
      c Positions of functional groups and DBs determined by independent techniques such as chromatographic resolution, ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      d Annotation using low resolution MS QQQ and a PIS m/z 184 requires the assumption of a sphingoid base with two hydroxyl groups.
      e Annotation with structural characterization of O-acyl in N-linked acyl chain.
      f Annotation without structural differentiation of N-linked acyl chain.
      TABLE 5DExamples for shorthand notation of glycosphingolipids containing an amide bound fatty acid
      PhylaSpecies Level
      Annotation based on exact mass measurements using a high-resolution mass spectrometer.
      Molecular Species Level
      Annotation requires MS/MS enabling detection of sphingoid base and/or N-linked FA.
      Full Structure Level
      Positions of functional groups and DBs determined by independent techniques such as chromatographic resolution, ozonolysis (8) or photochemical derivatization (9).
      MammalianHex-Cer 34:1;O2Hex-Cer 18:1;O2/16:0Glc-Cer(1) 18:1(4E);3OH/16:0 (see also Fig. 1)
      Glc-Cer 18:1;O2/16:0
      Separation of isomeric hexosylceramide by HILIC (36).
      MammalianHex-Cer 34:0;O2Hex-Cer 18:0;O2/16:0Gal-Cer(1) 18:0;3OH/16:0
      Gal-Cer 18:0;O2/16:0
      Separation of isomeric hexosylceramide by HILIC (36).
      MammalianHex2Cer 34:1;O2Hex2Cer 18:1;O2/16:0Lac-Cer(1) 18:1(4E);3OH/16:0
      Annotation requires separation of stereoisomers at glycosidic linkage (α/β).
      Gal-Glc-Cer(1) 18:1(4E);3OH/16:0
      MammalianHex3Cer 42:1;O2Hex3Cer 18:1;O2/24:0Gal-Gal-Glc-Cer(1) 18:1(4E);3OH/24:0 (= Gb3)
      MammalianNeuAcHex2Cer 42:1;O2NeuAcHex2Cer 18:1;O2/24:0NeuAc-Gal-Glc-Cer(1) 18:1(4E);3OH/24:0 (= GM3)
      MammalianNeuAc2Hex2Cer 42:1;O2NeuAc2Hex2Cer 18:1;O2/24:0NeuAc-NeuAc-Gal-Glc-Cer(1) 18:1(4E);3OH/24:0 (= GD3)
      MammalianSHex-Cer 34:1;O2SHex-Cer 18:1;O2/16:0S(3′)Hex-Cer(1) 18:1(4E);3OH/16:0
      S(3′)Gal-Cer(1) 18:1(4E);3OH/16:0
      Annotation requires separation of stereoisomers at glycosidic linkage (α/β).
      MammalianSHexHexNAcHex3Cer 34:1;O2SHexHexNAcHex3Cer 18:1;O2/16:0S(3′)Hex-HexNac-Hex-Hex-Hex-Cer(1) 18:1(4E);3OH/16:0
      S(3′)Gal-GalNAc-Gal-Gal-Glc-Cer(1) 18:1(4E);3OH/16:0
      Annotation requires separation of stereoisomers at glycosidic linkage (α/β).
      (globopentaosylceramide sulfate)
      PlantHexA-IPC 42:1;O4HexA-IPC 18:1;O3/24:0;OGlcA-IPC(1) 18:1(8E);3OH,4OH/24:0;2OH
      PlantHexHexA-IPC 42:1;O4Hex-HexA-IPC 18:1;O3/24:0;OGlc-GlcA-IPC(1) 18:1(8E);3OH,4OH/24:0;2OH
      PlantHexAHexNAc-IPC 42:1;O4HexNAc-HexA-IPC 18:1;O3/24:0;OGlcNAc-GlcA-IPC(1) 18:1(8E);3OH,4OH/24:0;2OH
      PlantHexHexAHexNAc-IPC 42:1;O4Hex-HexNAc-HexA-IPC 18:1;O3/24:0;OGlc-GlcNAc-GlcA-IPC(1) 18:1(8E);3OH,4OH/24:0;2OH
      YeastMIPC 44:0;O4MIPC 18:0;O3/26:0;OMIPC(1) 18:0;3OH,4OH/26:0;2OH
      YeastM(IP)2C 46:0;O4M(IP)2C 20:0;O3/26:0;OM(IP)2C(1) 20:0;3OH,4OH/26:0;2OH
      a Annotation based on exact mass measurements using a high-resolution mass spectrometer.
      b Annotation requires MS/MS enabling detection of sphingoid base and/or N-linked FA.
      c Positions of functional groups and DBs determined by independent techniques such as chromatographic resolution, ozonolysis (
      • Brown S.H.
      • Mitchell T.W.
      • Blanksby S.J.
      Analysis of unsaturated lipids by ozone-induced dissociation.
      ) or photochemical derivatization (
      • Ma X.
      • Chong L.
      • Tian R.
      • Shi R.
      • Hu T.Y.
      • Ouyang Z.
      • Xia Y.
      Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction.
      ).
      d Separation of isomeric hexosylceramide by HILIC (
      • von Gerichten J.
      • Schlosser K.
      • Lamprecht D.
      • Morace I.
      • Eckhardt M.
      • Wachten D.
      • Jennemann R.
      • Grone H.J.
      • Mack M.
      • Sandhoff R.
      Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals.
      ).
      e Annotation requires separation of stereoisomers at glycosidic linkage (α/β).

      STEROLS (ST)

      We use the term sterol to embrace all molecules based on the cyclopentanoperhydrophenanthrene skeleton. In the case of sterols, the ring system does not add to the number of DBE. Endogenously biosynthesized mammalian sterols are derived from cholesterol or its precursors, yet plant and yeast sterols can also be a source via the food chain. The stereochemistry of the cholesterol molecule is maintained to a large extent by mammalian sterols, which all contain at least one hydroxyl or oxo group attached to carbon 3. High resolution MS with accurate mass may identify other functional groups, as will MS/MS or MSn scans. Stereochemistry can often be defined by comparing the chromatographic retention time to authentic standards and, in some cases, by MS/MS or MSn. The class abbreviations within category ST are shown in Table 6A.
      TABLE 6AClass abbreviations in Category ST
      Common NameLipid Class, LIPID MAPSAbbreviation
      SterolsSterols [ST01]ST
      Sterol estersSterol esters [ST0102]SE
      Bile acidsBile acids and derivatives [ST04]BA
      Free cholesterol = cholesterolFC
      Cholesteryl esterCholesteryl esters [ST0102]CE
      SterylglycosidesSterylglycosidesSG
      AcylsterylglycosidesMonoradylglycosterolsASG
      The following rules for shorthand nomenclature have been adopted in the examples given in Table 6B.
      • In shorthand notation the category abbreviation ST is used as class abbreviation. In some cases, other abbreviations e.g., FC, CE, BA, SE, SG and ASG can be used. In all cases, class abbreviation is followed by number of carbon atoms:number of DB, and separated by semicolon is the number of oxygens, e.g., ST 27:1;O for cholesterol and lathosterol (also zymostenol), or ST 24:1;O5 for an oxidized sterol and for cholic acid and ursocholic acid. The latter is an important point: Some bile acids have an identical mass and molecular formula to oxidized sterols lacking a carboxylic acid group. This must be considered, when class abbreviation “BA” is used.
      • Shorthand notation of further functional groups are written, separated by a semicolon, after the number of oxygens, e.g., BA 24:1;O5;T for taurocholic acid (= common name, abbreviation TCA).
      • Following the number of double bonds, proven position and stereochemistry is shown. R and S configurations are preferred for side-chain stereochemistry and are shown in square brackets. α (below ring/plane), written as a, and β (above ring/plane), written as b, are preferred for ring stereochemistry, e.g. 3aOH and 17bOH. Stereochemistry at C-5 introduced by reduction of the Δ5 bond is indicated by 5aH or 5bH. Replacing the number of oxygens, proven positions and stereochemistry of oxygen containing functional groups are shown. If such stereochemistry is known the common name of the compound can be used.
      • The side-chain at carbon-17 of the cyclopentanoperhydrophenanthrene skeleton always has b-stereochemistry (17b) and consequently is not presented in the shorthand annotation.
      • For structures fully proven or based on assumption by biological intelligence, such as e.g., cholesterol, cholesteryl esters, steryl esters, bile acids, sterylglycosides, and acylsterylglycosides abbreviations FC, CE, SE, BA, SG and ASG, respectively, can be used as shown in Table 6A. CE is followed by number of C-atoms:number of DBE of the fatty acid esterified to the hydroxyl group at position 3, e.g., CE 18:2 (Table 6B). Shorthand notation SE is used as above followed by slash (for monohydroxysterols) or underscore (for polyhydroxysterols) number of C-atoms:number DBE of the fatty acid esterified to the hydroxyl group (Table 6B).
      • MS/MS scans reveal the presence of conjugates: Taurine (T) and glycine (G) each are conjugated through an amide bond to the carboxylic acid group of bile acids, respective amide bonds with conjugates are designated in shorthand notation “COT” and “COG” (Table 6B); sulfuric acid (S) is conjugated to a hydroxyl group through an ester bond; glucuronic acid (GlcA), N-acetylglucosamine (GlcNAc), and hexose (Hex) sugars are assumed to be linked to a hydroxyl group through an acetal linkage (Table 6B).
      • In the case full stereochemistry is known the common names as presented in Table 6B can be used.
      TABLE 6BExamples of shorthand notation for sterols
      Lipid ClassSpecies LevelFull Structure LevelComplete Structure Level (= Common Name)
      ST (FC)ST 27:1;OST 27:1(5Z);3bOH = FCCholesterol
      STST 27:1;OST 27:1(7);5aH;3bOHLathosterol
      STST 28:3;OST 28:3(5Z,7Z,22E);24Me[R];3bOHErgosterol
      STST 27:2;O3ST 27:1(5Z);3bOH;26COOH[25R]3β-Hydroxycholest-5-en-(25R)26-oic acid
      SESE 27:1/16:0CE 16:0Cholesteryl palmitate
      SESE 27:1/18:2CE 18:2(9Z,12Z)Cholesteryl linoleate
      SESE 27:2/18:1SE 27:2(8E,24);5aH/18:1(9Z)Zymosteryl oleate
      STST 21:3;O2ST 21:1(4Z);3oxo,20oxoProgesterone
      STST 19:2;O2ST 19:1(4Z);17bOH;3oxoTestosterone
      STST 19:2;O2ST 19:1(5Z);3bOH;17oxoDehydroepiandrosterone
      STST 18:3;O2ST 18:3(1,3,5);3OH,17bOH17β-Estradiol
      STST 19:2;O2;SST 19:1(5Z);3bS;17oxoDehydroepiandrosterone sulfate
      BAST 24:1;O5BA 24:0;5bH;3aOH,7aOH,12aOH;24COOHCholic acid (CA)
      BAST 24:1;O3BA 24:0;5bH;3aOH;24COOHLithocholic acid (LCA)
      BABA 24:1;O5;TBA 24:0;5bH;3aOH,7aOH,12aOH;24COTTaurocholic acid (TCA)
      BABA 24:1;O4;GBA 24:0;5bH;3aOH,7aOH;24COGGlycochenodeoxycholic acid (GCDCA)
      BAST 24:1;O4;HexNAcBA 24:0;5bH;3aOH,7bOGlcNAc;24COOHUrsodeoxycholic acid 7β-N-acetylglucosaminide (UDCA-GlcNac)
      SGSG 27:1;O;HexSG 27:1(5Z);3bOGlcCholesteryl glucoside
      ASGASG 29:2;O;Glc;FA20:3ASG 29:2(5Z,22E);24Et[S];3bOGlc;6O(FA 20:3)20:3(11Z,14Z,17Z)-Glc-stigmasterol

      DISCUSSION AND CONCLUSIONS

      This publication updates both the classification and nomenclature (
      • Fahy E.
      • Subramaniam S.
      • Brown H.A.
      • Glass C.K.
      • Merrill Jr., A.H.
      • Murphy R.C.
      • Raetz C.R.
      • Russell D.W.
      • Seyama Y.
      • Shaw W.
      • et al.
      A comprehensive classification system for lipids.
      ,
      • Fahy E.
      • Subramaniam S.
      • Murphy R.C.
      • Nishijima M.
      • Raetz C.R.
      • Shimizu T.
      • Spener F.
      • van Meer G.
      • Wakelam M.J.
      • Dennis E.A.
      Update of the LIPID MAPS comprehensive classification system for lipids.
      ) and shorthand notation (
      • Liebisch G.
      • Vizcaino J.A.
      • Köfeler H.
      • Trötzmüller M.
      • Griffiths W.J.
      • Schmitz G.
      • Spener F.
      • Wakelam M.J.
      Shorthand notation for lipid structures derived from mass spectrometry.
      ), and targets two goals. First, to emphasize and enable correct reporting of mass spectrometric data according to the resolving power of MS instrument platforms operating in high-resolution (and often high-throughput) mode. Second, to provide a comprehensible shorthand notation for the lipids commonly analyzed. Such common nomenclature is essential for standardized reporting of lipid species data and construction of data resources. Moreover, standardized data facilitate automated datamining and import into databases by script-based algorithms with only minimal data curation. Related data repositories require a hierarchical concept mirroring the structural resolution provided by mass spectrometric analysis reflected in the presented shorthand notation. To this end, the LMSD database, respective MS search tool, and, in particular, shorthand notations for all relevant lipids are now available on the LMSD detail view pages at “Species level” and “Molecular species level”, the latter embracing “Phosphate-”, “DB-”, and “sn-position level”. In a few instances, however, easy use of this shorthand notation by lipidomics experts has priority over its stringent use in a bioinformatics format.
      A standardized annotation for lipid species, as a common language, is a key component to promote and further advance this emerging omics discipline (
      • Liebisch G.
      • Ekroos K.
      • Hermansson M.
      • Ejsing C.S.
      Reporting of lipidomics data should be standardized.
      ). Therefore, the Lipidomics Standards Initiative (LSI; https://lipidomics-standards-initiative.org/) has been recently introduced (
      • Liebisch G.
      • Ahrends R.
      • Arita M.
      • Arita M.
      • Bowden J.A.
      • Ejsing C.S.
      • Griffiths W.J.
      • Holcapek M.
      • Köfeler H.C.
      • Mitchell T.W.
      • et al.
      Lipidomics Standards Initiative Consortium
      Lipidomics needs more standardization.
      ), pursuing development of guidelines and channeling community-wide efforts in close collaborations with LIPID MAPS (https://www.lipidmaps.org/) as has been emphasized recently (
      • O'Donnell V.B.
      • Ekroos K.
      • Liebisch G.
      • Wakelam M.
      Lipidomics: current state of the art in a fast moving field.
      ). In addition, alignment with other initiatives, as for example, adaptation of mzTab-M, a data format developed for metabolomics (
      • Hoffmann N.
      • Rein J.
      • Sachsenberg T.
      • Hartler J.
      • Haug K.
      • Mayer G.
      • Alka O.
      • Dayalan S.
      • Pearce J.T.M.
      • Rocca-Serra P.
      • et al.
      mzTab-M: A data standard for sharing quantitative results in mass spectrometry metabolomics.
      ), to the presented nomenclature is possible.
      In summary, the shorthand nomenclature presented here is viewed as a standard in lipidomics that can be updated periodically.

      Data availability

      All data are contained within this article.

      Acknowledgments

      The authors of this work are grateful to the UK's Wellcome Trust for its support (Grant 203014/Z/16/Z) of the LIPID MAPS expansion to the UK (2017–present), making it possible to continue the development of lipidomics and the International Lipid Classification and Nomenclature Committee (ILCNC) building on the earlier LIPID MAPS (Lipid Metabolites and Pathways Strategy) initiative funded by US National Institutes of Health Grant U54 GM069338 (2003–2017) and the European Union LipidomicNet Project Grant 202272 (2008–2013).

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