A specific, fast and sensitive LC–MS/MS assay was d e- veloped for the determination of bupropion and its me- tabolite hydroxybupropion in human plasma using lidocaine as the internal standard. The limit of qu antifica- tion was 3.13 ng/ml for bupropion and 7.81 ng/ml fo r hydroxybupropion. The method was linear in the stud ied range of 3.13 – 400.00 ng/ml for bupropion and 7.81 – 1000 ng/ml for hydroxybupropion. This analytical me thod was applied to a comparative pharmacokinetic study, in which seventy eight volunteers (39 men and 39 femal e) aged between 18 and 50 years received a single oral dose of 150 mg of reference and test bupropion formulati on, in an open, two-period, balanced randomized, crossover pro- tocol. Group 1 received the medication without any addi- tional meal. Group two received a hyperlipemic meal 30 min before the medication. Based on the 90% confide nce interval of the individual ratios for C max and AUC 0-inf , it was concluded that the test formulation is bioequiv alent to the reference formulation with respect to the ra te and extent of absorption of both bupropion and hydroxybupropion and that food intake before the dr ug administration had no effect in the relative pharma coki- netic parameters. However, the hyperlipemic meal si gnifi- cantly increased the bupropion absorption.