Development of a validated liquid chromatography-tandem mass spectrometry assay for the quantification of simvastatin acid, the active metabolite of simvastatin, in human plasma.
10.12793/tcp.2016.24.1.22
- Author:
Hyun Jung PARK
1
;
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
Author Information
1. Pharmacokinetic and Pharmacogenetic Laboratory, Clinical Research Center, Asan Medical Center, Pungnap-2-dong, Seoul, Republic of Korea.
- Publication Type:Original Article
- Keywords:
simvastatin acid;
plasma;
LC/MS/MS
- MeSH:
Adult;
Calibration;
Humans*;
Liquid-Liquid Extraction;
Lovastatin;
Male;
Mass Spectrometry*;
Methanol;
Plasma*;
Protons;
Quality Control;
Running;
Simvastatin*;
Volunteers
- From:Translational and Clinical Pharmacology
2016;24(1):22-29
- CountryRepublic of Korea
- Language:English
-
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.
