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. Metho...

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Bibliographic Details
Published in:Biopharmaceutics & drug disposition 2001-12, Vol.22 (9), p.383-390
Main Authors: Carvalho, M., Oliveira, C.H., Mendes, G.D., Sucupira, M., Moraes, M.E.A., De Nucci, G.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Amlodipine - blood
Amlodipine - chemistry
Amlodipine - pharmacokinetics
Antihypertensive agents
Antihypertensive Agents - blood
Antihypertensive Agents - chemistry
Antihypertensive Agents - pharmacokinetics
Biological and medical sciences
Cardiovascular system
Chemistry, Pharmaceutical
Chromatography, High Pressure Liquid - methods
Confidence Intervals
Cross-Over Studies
desipramine
Female
HPLC
Humans
LC-MS-MS
Linear Models
Male
Mass Spectrometry - methods
Medical sciences
pharmacokinetics
Pharmacology. Drug treatments
Tablets
Therapeutic Equivalency
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Summary: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: AUClast, AUC0–inf and Cmax. 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 AUClast, 99.6 (91.5–108.4%) for AUC0–inf and 98.5 (89.0–109.1%) for Cmax. Conclusion—Since the 90% CI for AUClast, AUC0–inf and Cmax 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.
ISSN:0142-2782
1099-081X
DOI:10.1002/bdd.282