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

다국어 초록 (Multilingual 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 mul-tiple 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/x². 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 chromato¬graphic running time was 3.0 min. This method sensitively and reliably measured SA concentra¬tions in human plasma and was successfully used in clinical pharmacokinetic studies of simvastatin in healthy Korean adult male volunteers.

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