Plasma samples (1 mL) containing internal standard (thiosalicylic acid, 1 µg) were acidified and extracted with dichloromethane (5 mL). The drug was then back extracted into 5% NaHCO3 (2 mL) followed by reacidification and reextraction into dichloromethane (2 mL). This extract was evaporated to dryness and the residue derivatised by the addition of pentafluorobenzylbromide (2% in acetone, 100 µL) in the presence of base. Following incubation at 60°C for 1 hour, the derivatising reagents were evaporated and the product dissolved in chloroform (200 µL). The derivatives were resolved on a 25 m length of 0. 2 mm ID HP-5 capillary column within 10 min following on-column injection. The HP 5971A mass spectrometer was tuned using the maximum sensitivity option and two fragment ions were monitored for both the captopril derivative (m/z 294, m/z 396) and the thiosalicylic acid derivative (m/z 333), m/z 514). The assay was linear from 10 to 5000 ng/mL with a captopril recovery of 77%. Assay precision at mean values of 45.9, 187 and 980 ng/mL were 4.0, 2.9 and 3.5 % respectively while accuracy was 8.2, 6.5 and 3.1 % across the assay range. Analysis of plasma samples from 20 volunteers following administration of 100 mg of captopril provided the following pharmacokinetic data (mean ± sd): Cmax, 1470 ± 467 ng/mL; AUC 0-inf., 1736 ± 481 ng/mL.h; Tmax 0.73 h; t1/2, 1.58 ± 0.41 h. We conclude that this assay is precise, accurate and robust and suitable for high throughput analysis of large batches of plasma samples such as those encountered in bioequivalence studies.