J. Lipid Res.
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A more recent version of this article appeared on October 1, 2006

Papers In Press, published online ahead of print July 21, 2006
J. Lipid Res., doi:10.1194/jlr.D600018-JLR200
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Submitted on May 15, 2006
Revised on July 21, 2006
Accepted on July 21, 2006

Validation of LC-MS/MS method for quantification of mevalonic acid in human plasma and an approach to differentiate recovery and matrix effect

G. S. Saini, T. A. Wani, A. Gautam, B. Varshney, T. Ahmed, K. S. Rajan, K. K. Pillai, and J. K. Paliwal

Ranbaxy Research Laboratories, Gurgaon, Haryana 122015

Corresponding Author: gurpreet.saini{at}ranbaxy.com

A simple, specific and sufficiently sensitive LC-MS/MS (negative-ion ESI) methodology to determine mevalonic acid (MVA) in human plasma is described, and its application to analysis of rat plasma MVA levels following rosuvastatin administration is demonstrated. The method was validated over the linearity range of 0.5-50.0 ng/mL (r2 > 0.99) using deuterated MVA (D7-MVA) as internal standard (IS). The lower limit of quantification (LLOQ) was 0.5 ng/mL. The assay procedure involved isolation of MVA from plasma samples using solid phase extraction. Chromatographic separation was achieved on a HyPurity Advance column with a mobile phase consisted of ammonium formate buffer (10 mM, pH 8.0) and acetonitrile (70:30, v/v). Excellent precision and accuracy was observed. MVA and deuterated mevalonolactone (D7-MVAL) were stable in water and plasma under different storage and processing conditions. The recovery observed was low, which was attributable to significant matrix effect. A significant decrease (30-40%, p < 0.05) was observed in rat plasma MVA levels following rosuvastatin administration.


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