Simultaneous determination of metformin and rosiglitazone in human plasma by LC-MS/MS and the pharmacokinetics studies

Aim: To establish an LC-MS/MS method to study the pharmacokinetics of metformin and rosiglitazone in human plasma. Methods: After adding phenformin, the internal standard, plasma samples were precipitated by acetonitrile and the supernatant was injected onto LC-MS/MS system. The chromatographic system consisted of Phenomenex Luna CN 100A column(150 mm × 2.0 mm ID) and the mobile phase of CH3OH-NH4Ac(30 mmol/L, pH 5.0) (80:20) at a flow rate of 0.2 mL/min. According to the crossover design using latin square, 12 volunteers orally received test capsules in single and multiple-dosing and plasma concentrations of metformin and rosiglitazone were determined by the validated method. Pharmacokinetic parameters of the two species were estimated. Results: The method exhibited linear ranges of from 5 to 3 000 ng,/mL and 1.5 to 500 ng/mL with a con-elation coefficient of 0.999 5 and 0.999 2 for metformin and rosiglitazone, respectively. The limit of detection was 1 ng/mL for both metformin and rosiglitazone. The concentration-time curves of metformin and rosiglitazone were best fitted to a two-compartment open model. Conclusion: The method is simple, sensitive and rapid. The absorption and disposition of metformin and rosiglitazone in human body follow the first order kinetics.