Amlodipine bioequivalence study: quantification by liquid chromatography coupled to tandem mass spectrometry.
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).


CONCLUSIONS
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.
Carvalho
M
M
Department of Pharmacology, State University of Campinas, UNICAMP, Brazil.
Oliveira
C H
CH
Mendes
G D
GD
Sucupira
M
M
Moraes
M E
ME
De Nucci
G
G
D000293:Adolescent; D000328:Adult; D017311:Amlodipine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016001:Confidence Intervals; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D013607:Tablets; D013810:Therapeutic Equivalency
D000959:Antihypertensive Agents; D013607:Tablets; D017311:Amlodipine