Determination of simvastatin in human plasma by HPLC-MS/MS and bioequivalence study in healthy volunteers
Lin Shu-guang · Central South Pharmacy · 2009
Objective To improve the determination of human plasma simvastatin,study the relative bioavailability of Simvastatin tablets,and evaluate the bioequivalence.Methods A single oral dose of 40 mg test and reference formulations was given to 20 healthy volunteers in a randomized cross-over study.Sample(0.2 mL) was determined by HPLC-MS/MS after being extracted by 1 mL diethyl ether.DAS 2.0 was used to assess the relative bioavailability and bioequivalence of Simvastatin tablets.Results The linear range of the calibration curves was 0.1~20 ng·mL-1 for simvastatin with a lower limit of quantitation(0.1 ng·mL-1).Within-and between-run precision was less than 6%.Accuracy ranged from 101% to 109%.The recovery was more than 82%.The main pharmacokinetic parameters t1/2,tmax,Cmax,AUC0~t and AUC0~∞ of the two formulations were as follows:(5.3±5.1)h,(2.2±0.7)h,(4.6±3.0)ng·mL-1,(24.3±15.7) ng·h ·mL-1,(27.5±21.6) ng·h ·mL-1 and(4.5±6.7)h,(1.9±0.7)h,(5.0±3.0) ng·mL-1,(21.4±13.4) ng·h ·mL-1,(23.9±21.2) ng·h ·mL-1.Relative bioavailability of Simvastatin test reference was 113.1%±17.4%.Conclusion The present method is sensitive and reliable.The method described herein has been successfully used for the bioequivalence study of simvastatin formulation.The test and reference simvastatin tablets are bioequivalent.