Determination of CGS 16617 and stable isotope-labeled CGS 16617, an angiotensin-converting enzyme inhibitor, in human plasma by gas chromatography/mass spectrometry.
An analytical method has been developed for the simultaneous determination of a novel orally active angiotensin-converting enzyme inhibitor (CGS 16617) and a stable isotope-labeled analog. Both compounds are isolated from human plasma using an ion-exchange column, derivatized with pentafluoropropionic anhydride and pentafluoropropanol, and analyzed by gas chromatography/mass spectrometry. After splitless injection on a methyl-silicon column, the compound is detected using negative ion chemical ionization with nitrous oxide as a reagent gas. CGS 16617 labeled with four deuteriums and two 13C is used as an internal standard. The accuracy and precision of the method, expressed as the overall mean +/- SD recovery obtained from two sets of 36 quality-control samples used during a clinical study (concentration range 0.2-100 ng ml-1 plasma), was 96.1 +/- 16.2% for unlabeled drug and 97.6 +/- 14.4% for the D4-labeled drug (concentration range 0.2-100 ng ml-1 plasma). The limit of quantification using 1 ml plasma is 0.2 ng ml-1 for both labeled and unlabeled drug.
Gaudry
D
D
Drug Development Department, CIBA-GEIGY Corporation, Ardsley, New York.
Hayes
M
M
Khemani
L
L
Miotto
J
J
Alkalay
D
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood*; D001552:Benzazepines / Q000097:blood*; D002247:Carbon Isotopes; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D007553:Isotope Labeling
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D002247:Carbon Isotopes; D003903:Deuterium; C052134:libenzapril