An open-label, randomised, crossover single dose study, using 2 periods x 2 sequences, with a minimum washout period of 4 weeks, was conducted in order to assess the comparative bioavailability of two formulations of sertraline hydrochloride (CAS 79617-96-2) 100 mg tablets. Plasma samples were obtained at intake (baseline) and at +1 h, +2 h, +3 h, +4 h, +5 h, +6 h, +7 h, +8 h, +9 h, +12 h, +24 h, +48 h, +72 h and +96 h post administration. Sertraline plasma concentrations were determined by high pressure liquid chromatography with tandem mass detection (HPLC-MS/MS) and the lower limit of quantification was set at 100.15 pg/mL. Pharmacokinetic parameters used for bioequivalence assessment (AUClast, AUCinf and Cmax) were determined by non-compartmental analysis. Classical 90 % confidence intervals (90CI) were calculated for the overall sample, and for males and females separately, and gender effects were investigated using an appropriate model. The results showed that overall classical 90CI were 84.55-100.32 % for Cmax 86.96-98.68 % for AUClast, and 86.79-98.93 for AUCinf, that is, they were all within the predefined ranges for bioequivalence acceptance. Separate gender analysis showed very similar results for males and females when analysed independently, and no gender effects were detected in bioequivalence analysis (p > 0.05). It may be therefore concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption.