Determination of lamivudine in human plasma by LC-MS/MS and its bioequivalence

Objective To establish an LC-MS/MS method to determine lamivudine in human plasma and to study the bioavailability and bioequivalence of the test and reference lamivudine tablets in healthy male volunteers.Methods A single oral dose(100 mg) of test tablets or reference tablets was given to each volunteer according to an open randomized crossover study.The concentrations in the plasma were determined by LC-MS/MS method.The pharmacokinetic parameters were calculated by WinNonlin 6.1 software.Results The calibration curve of lamivudine showed good linearity at 20.48-5 000 μg L-1.The LLOQ of lamivudine was 20.48 μg L-1.The main pharmacokinetic parameters of lamivudine were as follows: Cmax(1 152.6±326.4) and(1 032.4±319.7) μg L-1;tmax(0.93±0.30) and(1.07±0.47) h;t1/2(3.4±0.7) and(3.3±0.6) h;AUC0 ～ 16 h(3 811.9±870.2) and(3 753.6±1 067.0) μg h L-1;AUC0 ～∞(3 958.9±871.3) and(3 914.8±1 087.0) μg h L-1for the reference and test preparations,respectively.The relative bioavailability of test tablets was(98.2±17.0)%.Conclusion The method is simple,rapid,sensitive and accurate,which can be used to detect the concentration of lamivudine in human plasma.The two lamivudine preparations are bioequivalent.