IMPROVED ANALYTICAL PROCEDURE FOR THE MEASUREMENT OF CAPTOPRIL IN HUMAN PLASMA BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY AND ITS APPLICATION TO PHARMACOKINETIC STUDIES

An enhanced, sensitive CC-MS assay is presented for the highly specifi c angiotensin-converting enzyme (ACE) inhibitor, captopril. This metho d improves previously published assays by using solid NEM as stabilize r in the collection tubes, a rapid extraction technique with dichlorom ethane and back-extraction into base, a commercially available interna l standard (thiosalicylic acid) and a capillary GC column. Captopril a nd the internal standard are measured as their bis-pentafluorobenzyl d erivatives. The assay was linear from 10 to 5000 ng/ml with a mean rec overy following solvent extraction at 50, 200 and 1000 ng/ml of 77%. A t mean values of 45.9, 187 and 980 ng/ml inter assay precision and acc uracy were 4.0, 2.9 and 3.5% and 8.2, 6.5 and 3.1%, respectively. Anal ysis of captopril concentrations in plasma samples from 20 volunteers following oral administration of 100 mg of captopril provided the foll owing pharmacokinetic data (mean +/- S.D.): C-max,,,, 1470 +/- 467 ng/ ml; AUC(0-infinity), 1736 +/- 481 ng/ml.h; T-max, 0.73 h; k(e), 0.468 +/- 0.122 h(-1); elimination half life, 1.58 +/- 0.41 h. (C) 1998 Else vier Science B.V.