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Amlodipine bioequivalence study: quantification by liquid chromatography coupled to tandem mass spectrometry
Author(s) -
Carvalho M.,
Oliveira C.H.,
Mendes G.D.,
Sucupira M.,
Moraes M.E.A.,
De Nucci G.
Publication year - 2001
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.282
Subject(s) - bioequivalence , amlodipine , pharmacokinetics , chromatography , chemistry , confidence interval , crossover study , liquid chromatography–mass spectrometry , pharmacology , mass spectrometry , medicine , alternative medicine , pathology , blood pressure , placebo
Objective —To assess the bioequivalence of two amlodipine tablet formulations (Amlodipine ® 5 mg tablet from Merck S.A. Indústrias Químicas, Brazil as test formulation and Norvasc ® 5 mg tablet from Laboratórios 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 amlodipine 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% CI 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 ® 5 mg tablet (test formulation) was bioequivalent to Norvasc ® 5 mg tablet, in terms of both rate and extent of absorption. Copyright © 2001 John Wiley & Sons, Ltd.