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Journal of Lipid Research, Vol 31, 1445-1454, Copyright © 1990 by Lipid Research, Inc.
C Eckhoff and H Nau
Human plasma was analyzed by high performance liquid chromatography for the
presence of retinoic acid and 4-oxoretinoic acid isomers. Peaks that
coeluted with the reference compounds all-trans-retinoic acid, 13-
cis-retinoic acid, and 13-cis-4-oxoretinoic acid were routinely observed in
human plasma. These retinoids were unequivocally identified by the
following methods: comigration with reference compounds under several high
performance liquid chromatographic conditions; comparison of ultraviolet
spectra with those of reference compounds; derivatization with diazomethane
and coelution of the methyl esters with reference compounds in a high
performance liquid chromatographic system as well as in a gas
chromatography system with a mass selective detector. In vitro formation of
13-cis-retinoic acid and 13-cis-4- oxoretinoic acid as artifacts during the
analytical procedure was excluded by control experiments. The mean plasma
concentrations of the vitamin A metabolites in ten male volunteers were:
all-trans-retinoic acid: 1.32 +/- 0.46 ng/ml; 13-cis-retinoic acid: 1.63
+/- 0.85 ng/ml; and 13-cis-4-oxoretinoic acid: 3.68 +/- 0.99 ng/ml. After
oral dosing with vitamin A (833 IU/kg body weight) in five male volunteers,
mean plasma all-trans-retinoic acid increased to 3.92 +/- 1.40 ng/ml and
13- cis-retinoic acid increased to 9.75 +/- 2.18 ng/ml. Maximal plasma 13-
cis-4-oxoretinoic acid concentrations (average 7.60 +/- 1.45 ng/ml) were
observed 6 h after dosing which was the last time point in this study.
Concentrations of all-trans-4-oxoretinoic acid were low or not detectable.
Our findings suggest that, in addition to all-trans- retinoic acid,
13-cis-retinoic acid and 13-cis-4-oxoretinoic acid are present in normal
human plasma as metabolites of vitamin A.
ARTICLES
Identification and quantitation of all-trans- and 13-cis-retinoic acid and 13-cis-4-oxoretinoic acid in human plasma
Institut fur Toxikologie und Embryonalpharmakologie, Freie Universitat Berlin, West Germany.
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