Quantification of lamivudine in human plasma by hydrophilic interaction chromatography-tandem mass spectrometry

A rapid, selective and sensitive method for the determination of lamivudine in human plasma was developed using hydrophilic interaction chromatography-MS/MS. This method involved protein precipitation with acetonitrile as sample preparation procedure. Lamivudine and famotidine (internal standard) were analyzed on a Luna hydrophilic interaction chromatography column with the mobile phase of acetonitrile/10 mM ammonium formate (95:5, v/v) and detected using electrospray ionization mass spectrometry in the selected reaction monitoring mode. The standard curve was linear (r(2)=0.9985) over the concentration range of 50-3000 ng/mL. The lower limit of quantification was 50 ng/mL using 50 microL of plasma sample. The coefficient of variation and relative error for intra- and inter-assay at four quality control levels were 2.1-7.5 and -4.0 to 3.3%, respectively. The absolute and relative matrix effects for lamivudine and famotidine were practically absent. The present method was successfully applied to the pharmacokinetic study of lamivudine after oral dosing of lamivudine (100 mg tablet) to male healthy volunteers.