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2016 (v.24 no.1)

Translational and Clinical Pharmacology

Korean Society for Clinical Pharmacology and Therapeutics
Quarter
ISSN: 2289-0882

  • Development of a validated liquid chromatography-tandem mass spectrometry assay for the quantification of simvastatin acid, the active metabolite of simvastatin, in human plasma

    Hyun-Jung Park, Ae-Kyung Hwang, A-Reum Kim, Soo-Hyeon Kim, Eun-Hwa Kim, Sang-Heon Cho, Jong-Lyul Ghim, Sangmin Choe, Jin-Ah Jung, Seok-Joon Jin, Kyun-Seop Bae, Hyeong-Seok Lim

    TCP | v.24, no.1, pp.22-29, Mar, 2016

    Abstract

    Simvastatin is a lipid-lowering drug that is metabolized to its active metabolite simvastatin acid(SA). We developed and validated a sensitive liquid chromatography-tandem mass spectrometry(LC/MS/MS) method to quantitate SA in human plasma using a liquid-liquid extraction methodwith methanol. The protonated analytes generated in negative ion mode were monitored by multiple reaction monitoring. Using 500-mL plasma aliquots, SA was quantified in the range of 0.1-100ng/mL. Calibration was performed by internal standardization with lovastatin acid, and regressioncurves were generated using a weighting factor of 1/x². The linearity, precision, and accuracy of thisassay for each compound were validated using quality control samples consisting of mixtures of SA(0.1, 0.5, 5, and 50 ng/mL) and plasma. The intra-batch accuracy was 95.3-107.8%, precision was-2.2% to -3.7%, and linearity (r²) was over 0.998 in the standard calibration range. The chromatographic running time was 3.0 min. This method sensitively and reliably measured SA concentrations in human plasma and was successfully used in clinical pharmacokinetic studies of simvastatin in healthy Korean adult male volunteers.

    Keyword

    simvastatin acid, plasma, LC/MS/MS