Journal of Chromatography B 2015-03-01

Liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of simvastatin, lovastatin, atorvastatin, and their major metabolites in human plasma.

Jiang Wang, Jasmine A Luzum, Mitch A Phelps, Joseph P Kitzmiller

文献索引：J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 983-984 , 18-25, (2015)

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摘要

Millions of individuals are treated with a variety of statins that are metabolized to a variety of active metabolites. A single assay capable of simultaneously quantifying commonly used statins and their major metabolites has not been previously reported. Herein we describe the development and validation of a novel and robust liquid chromatography-tandem mass spectrometry assay for simultaneously quantifying simvastatin, lovastatin, atorvastatin, and their metabolites, simvastatin acid, lovastatin acid, para-hydroxy atorvastatin, and ortho-hydroxy atorvastatin in human plasma. Plasma samples were processed with a simple protein precipitation technique using acetonitrile, followed by chromatographic separation using an Agilent Zorbax Extend C18 column. A 12.0min linear gradient elution was used at a flow rate of 400μL/min with a mobile phase of water and methanol, both modified with 2mM ammonium formate and 0.2% formic acid. The analytes and internal standard, hesperetin, were detected using the selected reaction monitoring mode on a TSQ Quantum Discovery mass spectrometer with positive electrospray ionization. The assay exhibited a linear range of 1-1000nM for simvastatin acid and lovastatin acid, and a linear range of 0.1-100nM for the other analytes in human plasma. The accuracy and the within- and between-day precisions of the assay were within acceptable ranges, and the method was successfully utilized to quantify the statins and their metabolites in human plasma samples collected from an ongoing pharmacokinetic study. Copyright © 2015 Elsevier B.V. All rights reserved.