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 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.): Cmax, 1470+/-467 ng/ml; AUC(0-infinity), 1736+/-481 ng/ml.h; Tmax, 0.73 h; k(e), 0.468+/-0.122 h(-1); elimination half life, 1.58/-0.41 h.
Franklin
M E
ME
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Australia.
Addison
R S
RS
Baker
P V
PV
Hooper
W D
WD
D000284:Administration, Oral; D000328:Adult; D000803:Angiotensin I / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002216:Captopril / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D000803:Angiotensin I; D002216:Captopril