Improved analytical procedure for the measurement of captopril in human plasma by gas chromatography–mass spectrometry and its application to pharmacokinetic studies

• Published in: Journal of chromatography. B, Biomedical sciences and applications Biomedical sciences and applications, 1998-01, Vol.705 (1), p.47-54
• Main Authors: Franklin, M.E, Addison, R.S, Baker, P.V, Hooper, W.D
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Analysis; Angiotensin I - metabolism; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - blood; Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics; Biological and medical sciences; Captopril; Captopril - administration & dosage; Captopril - blood; Captopril - pharmacokinetics; Gas Chromatography-Mass Spectrometry; General pharmacology; Humans; Medical sciences; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity
• ISSN: 0378-4347; 1387-2273
• DOI: 10.1016/S0378-4347(97)00481-7

An enhanced, sensitive GC–MS assay is presented for the highly specific angiotensin-converting enzyme (ACE) inhibitor, captopril. This method improves previously published assays by using solid NEM as stabilizer in the collection tubes, a rapid extraction technique with dichloromethane and back-extraction into base, a commercially available internal standard (thiosalicylic acid) and a capillary GC column. Captopril and the internal standard are measured as their bis-pentafluorobenzyl derivatives. The assay was linear from 10 to 5000 ng/ml with a mean recovery following solvent extraction at 50, 200 and 1000 ng/ml of 77%. At mean values of 45.9, 187 and 980 ng/ml inter-assay precision and accuracy were 4.0, 2.9 and 3.5% and 8.2, 6.5 and 3.1%, respectively. Analysis of captopril concentrations in plasma samples from 20 volunteers following oral administration of 100 mg of captopril provided the following pharmacokinetic data (mean±S.D.): C max, 1470±467 ng/ml; AUC 0–∞, 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.