title: Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism.
abstract: Isotope ratio (IR) mass spectrometry was evaluated for the study of drug metabolism and balance using 13C, 15N2-labelled antipyrine (AP) as a test drug. Rats were given 40 mg kg-1 (13C,15N2)AP intraperitoneally. Breath, urine, faeces and blood were collected. Except for breath, samples were combusted in sealed quartz tubes. The resulting CO2 and N2 were analysed for excess 13C and 15N, relative to pre-dose samples, by IR mass spectrometry. In addition, blood levels of AP and cumulative excretion of urinary AP metabolites were determined by gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) and high-performance liquid chromatography (HPLC) respectively. Excess 13C and 15N levels in blood were comparable with observed levels of AP, and urinary recoveries of 13C (42%) were in good agreement with those calculated from HPLC data (45%). N-Demethylation, one of the important pathways of AP metabolism, was most rapidly determined by excess 13CO2 excretion in breath (8%). The IR mass spectral analysis complemented gas chromatographic/mass spectrum and HPLC analyses, and was less complex.
authors.forename: A
authors.initials: A
authors.lastname: Nakagawa
authors.forename: A
authors.initials: A
authors.lastname: Kitagawa
authors.forename: M
authors.initials: M
authors.lastname: Asami
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: D A
authors.initials: DA
authors.lastname: Schoeller
authors.forename: R
authors.initials: R
authors.lastname: Slater
authors.forename: M
authors.initials: M
authors.lastname: Minagawa
authors.forename: I R
authors.initials: IR
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D008111:Liver Function Tests; D008297:Male; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013055:Spectrophotometry, Infrared
chemical_list: D004364:Pharmaceutical Preparations; D000983:Antipyrine