Determination of a new angiotensin-converting enzyme inhibitor (CS-622) and its active metabolite in plasma and urine by gas chromatography-mass spectrometry using negative ion chemical ionization.
A sensitive and specific gas chromatographic-mass spectrometric method for the simultaneous determination of angiotensin-converting enzyme inhibitor (I, CS-622) and its active desethyl metabolite (II, RS-5139) in plasma and urine was developed. Compound D5-RS-5139 was used as an internal standard and measurements were made by electron-capture negative ion chemical ionization. Extraction from plasma and urine was carried out using Sep-Pak C18 and silica cartridges. The extract of plasma or urine was treated with diazomethane followed by trifluoroacetic anhydride to convert I and II into their methyl ester trifluoroacetyl derivatives. The detection limit of I and II was 0.5 ng/ml in plasma and 5 ng/ml in urine. The proposed method was satisfactory for the determination of I and II in plasma and urine with respect to accuracy and precision. Thus it is suitable for measurement of bioavailability and pharmacokinetics of I and II in body fluids.
Shioya
H
H
Product Development Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Shimojo
M
M
Kawahara
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000378:metabolism* / Q000652:urine; D055598:Chemical Phenomena; D002621:Chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D013841:Thiazepines / Q000097:blood / Q000378:metabolism* / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; C055603:temocapril hydrochloride