By nature of their nucleophilicity, all thiol-based drugs are oxidatively metabolized in the physiological environment. The key to understanding the physiological role of a hypertension drug, (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid, medically known as captopril is through studying its oxidation pathway: its reactive intermediates and oxidation products. The oxidation of captopril by aqueous bromine and acidified bromate has been studied by spectrophotometric and electrospray ionization techniques. The stoichiometry for the reaction of acidic bromate with captopril is 1:1, BrO3(-) + (C4H6N)(COOH)(COCHCH3CH2)-SH → (C4H6N)(COOH)(COCHCH3CH2)-SO3H + Br(-), with reaction occurring only at the thiol center. For the direct reaction of bromine with captopril, the ratio is 3:1; 3Br2 + (C4H6N)(COOH)(COCHCH3CH2)-SH + 3H2O → (C4H6N)(COOH)(COCHCH3CH2)-SO3H + 6HBr. In excess acidic bromate conditions the reaction displays an initial induction period followed by a sharp rise in absorbance at 390 nm due to rapid formation of bromine. The direct reaction of aqueous bromine with captopril was much faster than oxidation of the thiol by acidified bromate, with a bimolecular rate constant of (1.046 (±0.08) × 10(5) M(-1) s(-1). The detection of thiyl radicals confirms the involvement of radicals as intermediates in the oxidation of Captopril by acidified BrO3(-). The involvement of thiyl radicals in oxidation of captopril competes with a nonradical pathway involving 2-electron oxidations of the sulfur center. The oxidation product of captopril under these strong oxidizing conditions is a sulfonic acid as confirmed by electrospray ionization mass spectrometry (ESI-MS), iodometric titrations, and proton nuclear magnetic resonance ((1)H NMR) results. There was no evidence from ESI-MS for the formation of the sulfenic and sulfinic acids in the oxidation pathway as the thiol group is rapidly oxidized to the sulfonic acid. A computer simulation analysis of this mechanism gave a reasonably good fit to the experimental data.