Mixtures of thiuram disulfides are frequently used as accelerators in rubber stoppers for injectables and sterilized powders for injection. Rapid reactions of thiuram disulfides between themselves and with thiols yield mixed disulfides due to thiol–disulfide exchange. The possibility of exchange reactions of thiuram disulfides extracted from rubber stoppers and drug products containing pendant thiol groups have not been reported in the analysis of potential stopper extractables. In this paper we report the formation and identification of mixed thiuram disulfides of N, N, N′, N′-dimethylthiuram disulfide (TMTD), N, N, N′, N′-dibutylthiuram disulfide (TBTD), and captopril (a thiol-containing drug). A reversed-phase HPLC method was developed for the determination of TMTD, TBTD, captopril and their disulfides in aqueous vehicles, using a YMC ODS AQ column at 35 °C and mobile phases A and B consisting of acetonitrile:water:trifluoroacetic acid (TFA) (20:80:0.1) and acetonitrile:TFA (100:0.1), respectively. The captopril–TBTD and captopril–TMTD disulfides were identified by MS, with molecular ions at m/ z 420.9 and m/ z of 337.1, respectively. Possible structures for the fragment ions in the spectra are provided. Mixed captopril–thiuram formation was studied as a function of pH. Captopril–TMTD formation was enhanced at pH 6.0, reaching a maximum of 31.3% in 4.1 h. At pH 4.0 and 2.2, the mixed captopril adduct product was still detected in solution after 20 h. The impact of the formation of mixed disulfide products of thiol-containing drugs with thiurams in the HPLC profile of extractables and leachables studies is discussed.