Atenolol quantification in human plasma by high-performance liquid chromatography: application to bioequivalence study.
An accurate, precise, and sensitive high-performance liquid chromatography (HPLC) assay was developed for the determination of atenolol in human plasma samples to compare the bioavailability of 2 atenolol tablet (50 mg) formulations in 24 volunteers of both sexes. The study had an open, randomized, 2-period crossover design with a 1-week washout period. Plasma samples were obtained over a 24-hour interval. Atenolol concentrations were analyzed by combined reversed phase liquid chromatography and fluorescence detection (lambda(EX) = 258 nm, lambda(EM) = 300 nm). From the atenolol plasma concentration versus time curves, the following pharmacokinetic parameters were obtained: AUC(0-24h), AUC(0- infinity ), and C(max). The geometric mean of test/reference 50-mg tablets individual percent ratio was 102.2% for AUC(0-24h), and 101.6% for C(max). The 90% confidence intervals (CI) were 100.2% to 105.4% and 100.9% to 103.5%, respectively. Since the 90% CI for both C(max) and AUC(0-24h) were within the 80% to 125% interval proposed by the Food and Drug Administration, it was concluded that atenolol (50-mg tablets) test formulation was bioequivalent to the reference formulation, with regard to both the rate and extent of absorption.
de Abreu
Luis Renato Pires
LR
Department of Pharmacology, Faculty of Medical Sciences-UNICAMP, Campinas, São Paulo, Brazil. lrpabreu@uol.com.br
de Castro
Silvana Aparecida Calafatti
SA
Pedrazzoli
José
J
D000959:Antihypertensive Agents / Q000097:blood*; D001262:Atenolol / Q000097:blood*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D011786:Quality Control; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013607:Tablets; D013810:Therapeutic Equivalency
D000959:Antihypertensive Agents; D013607:Tablets; D001262:Atenolol