Abstract:

A rapid, sensitive and specific method has been developed for the determination of simvastatin in human plasma with ultra-performance liquid chromatography-tandem mass spectrometry. Simvastatin and the internal standard （lovastatin） were extracted from human plasma with diethyl ether-n-hexane-isopropanol (80∶20∶3, v/v/v), then separated on a Waters ACQUITY UPLCTM BEH C18 column (50 mm×2.1 mm, 1.7 μm) with isocratic elution at a flow rate of 0.25 mL/min. The mobile phase was composed of 85% acetonitrile and 15% water (containing 10 mmol/L ammonium acetate). Electrospray ionization (ESI) source was applied and operated in positive ion mode. Multiple reaction monitoring (MRM) mode with the transitions of m/z 419.2 →m/z 199.0 and m/z 405.0→m/z 199.0 was used to quantify simvastatin and the internal standard, respectively. The linear calibration curve was obtained in the concentration range of 0.051-20.4 ng/mL. The lower limit of quantification was 0.051 ng/mL. The inter-day and intra-day precision (relative standard deviation) were less than 10%, and the accuracy (relative error) was within -2.7%-0% calculated from quality control samples. The mean extraction recovery of simvastatin was 91.6%. The method was proved to be selective, sensitive, rapid and suitable for the pharmacokinetic study of simvastatin.

Key words: plasma concentration
, simvastatin, ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）