Amlodipine Bioequivalence study: Quantification by liquid chromatography coupled to tandem mass spectrometry

Objective-To assess the bioequivalence of two amlodipine tablet formulations (Amlodipine(R) 5 mg tablet from Merck S.A. Industrias Quimicas, Brazil as test formulation and Norvasc(R) 5 mg tablet from Laboratorios Pfizer Ltd., Brazil as reference formulation) in 24 healthy volunteers of both sexes. Methods-The study Was conducted using an open, randomized two-period crossover design with a 4-week washout interval. Plasma samples were obtained over a 144 h period. Plasma amlodipine concentrations were analyzed by combined liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the amiodipine plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C-max. The statistical interval proposed was 80-125% according to the US Food and Drug Administration Agency. Results-The limit of quantification was 0.1 ng/ml for plasma amlodipine analysis. The geometric mean and the 90% confidence interval (CI) test/reference ratios were 101.2 (92.9-110.2%) for AUC(last), 99.6 (91.5-108.4%) for AUC(0-inf), and 98.5 (89.0-109.1%) for C-max. Conclusion-Since the 90% Cl for AUC(last), AUC(0-inf) and C-max ratios were within in the 80-125% interval proposed by the US FDA, it was concluded that Amlodipine(R) 5 mg tablet (test formulation) was bioequivalent to Norvasc(R) 5 mg tablet, in terms of both rate and extent of absorption. Copyright (C), 2001 John Wiley Sons, Ltd.