Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism
Article first published online: 11 APR 2005
Copyright © 1985 John Wiley & Sons, Ltd.
Biological Mass Spectrometry
Volume 12, Issue 9, pages 502–506, September 1985
How to Cite
Nakagawa, A., Kitagawa, A., Asami, M., Nakamura, K., Schoeller, D. A., Slater, R., Minagawa, M. and Kaplan, I. R. (1985), Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism. Biol. Mass Spectrom., 12: 502–506. doi: 10.1002/bms.1200120911
- Issue published online: 11 APR 2005
- Article first published online: 11 APR 2005
- Manuscript Revised: 30 JUL 1984
- Manuscript Received: 18 MAY 1984
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.