Determination of a new angiotensin converting enzyme inhibitor and its active metabolite in plasma and urine by gas chromatography-mass spectrometry.
A specific and sensitive gas chromatographic-mass spectrometric method for the simultaneous quantification of unchanged 3-[( 1-ethoxycarbonyl-3-phenyl-(1S)-propyl]amino)-2,3,4,5-tetrahydro-2-oxo-1- 1-(3S)-benzazepine-1-acetic acid (I) and its active metabolite, the dicarboxylic acid (II), in plasma and urine has been developed and validated. 2H5-labelled analogues of I and II were used as internal standards. The compounds were isolated from plasma and urine under acidic conditions using XAD-2 resin or Extrelut 1 columns. Following derivatization with diazomethane, the samples were analysed by packed-column gas chromatography-electron-impact mass spectrometry with selected-ion monitoring. The analysis of spiked plasma and urine samples demonstrated the good accuracy and precision of the method, which is suitable for use in pharmacokinetic and bioavailability studies with the new angiotensin converting enzyme inhibitor prodrug I.HCl in humans.
Kaiser
G
G
Research and Development Department, Ciba-Geigy Limited, Basle, Switzerland.
Ackermann
R
R
Dieterle
W
W
Dubois
J P
JP
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001552:Benzazepines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007202:Indicators and Reagents
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D007202:Indicators and Reagents; C044946:benazepril