A bioequivalence study of citalopram based on quantification by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry

Objective: The aim of this study was to compare the bioavailability of two citalopram formulations (citalopram from Eurofarma Laboratorios Ltda., as the test formulation, and cipramil from Schering-Plough, Brazil, as the reference formulation) in healthy volunteers. Methods: The study had an open, randomized, two-period crossover design with a two-week washout interval between doses. The samples were obtained over a 168-hour interval after each oral administration of citalopram (one 20 mg tablet of each formulation). The analyte and the internal standard were extracted from plasma using diethylether : dichloromethane (70 : 30, v/v) and the extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Chromatography was done isocratically using a Genesis C8 analytical column (4 pm, 2.1 mm i.d. x 100 mm). The method had a chromatographic run time of three minutes and a linear calibration curve over the range of 0.5-200 ng x ml(-1) (r(2) > 0.999887). The limit of quantification was 0.5 ng x ml(-1). Results: The geometric mean and 90% confidence intervals (Cl) for the citalopram/cipramil ratio were 98.28% (94.24-102.49%) for AUC(last), 96.44% (90.20-103.11%) for AUC(inf), and 98.54% (94.70-102.54%) for C-max, Conclusion: Since the 90% Cl for C-max, AUC(last) and AUC((0-infinity)) ratios were all within the 80 - 125% interval proposed by the US Food and Drug Administration, we concluded that the citalopram formulation elaborated by Eurofarma Laboratorios Ltda. was bioequivalent to the cipramil formulation in its rate and extent of absorption.43838939