OBJECTIVE To compare the bioavailability of 2 sertraline tablets formulations (Tolrest from Laboratórios Biosintética, and Zoloft from Laboratórios Pfizer, Brazil) in 24 healthy volunteers of both sexes (12 male and 12 female) who received a single 50 mg dose of each sertraline formulation. METHODS The study was conducted open with randomized two-period crossover design and a 14-day washout period. Plasma samples were obtained over a 96-hour interval and sertraline concentrations were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using selected ion monitoring method. From the plasma sertraline concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(0-96h), AUC(0-infinity), Cmax, Cmax/AUC(0-96h), Tmax, ke, and t(1/2). RESULTS Pharmacokinetic parameters presented normal distribution according to Probit' s plot and Kolmogorov Smirnov's test, and the variance of AUC(0-96h), AUC(0-infinity) or Cmax were homoscedastic. Geometric mean Tolrest/Zoloft individual percent ratio was 95.22% for AUC(0-96h), 99.87% for Cmax, 100.4% for AUC(0-infinity), 103.6% for Ke, 96.0% for t(1/2) and 93.7% for Tmax. CONCLUSIONS Since the 90% CI for both Cmax and AUC(0-96h) mean ratio were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that Tolrest was bioequivalent to Zolof for both extent and rate of absorption in a single dose administration.