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Transl Clin Pharmacol. 2016 Mar;24(1):22-29. English. Original Article. https://doi.org/10.12793/tcp.2016.24.1.22
Park HJ , Hwang AK , Kim AR , Kim SH , Kim EH , Cho SH , Ghim JL , Choe S , Jung JA , Jin SJ , Bae KS , Lim HS .
Pharmacokinetic and Pharmacogenetic Laboratory, Clinical Research Center, Asan Medical Center, Pungnap-2-dong, Seoul, Republic of Korea.
Department of Clinical Pharmacology, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea.
Department of Pharmacology, Inje University College of Medicine, Busan, Republic of Korea.
Division of Clinical Pharmacology, Clinical Trials Center, Pusan National University Hospital, Busan, Republic of Korea.
Department of Anesthesiology, University of Ulsan College of Medicine, Asan Medical Center, Pungnap-2-dong, Seoul, Republic of Korea.
Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Republic of Korea, Seoul, Republic of Korea. mdhslim@gmail.com
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 method with 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 0.1-100 ng/mL. Calibration was performed by internal standardization with lovastatin acid, and regression curves were generated using a weighting factor of 1/χ2. The linearity, precision, and accuracy of this assay 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.

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