Application of high-performance liquid chromatography/chemical reaction interface mass spectrometry for the analysis of conjugated metabolites: A demonstration using deuterated acetaminophen
Article first published online: 11 APR 2005
Copyright © 1994 John Wiley & Sons, Ltd.
Biological Mass Spectrometry
Volume 23, Issue 12, pages 776–783, December 1994
How to Cite
Teffera, Y. and Abramson, F. (1994), Application of high-performance liquid chromatography/chemical reaction interface mass spectrometry for the analysis of conjugated metabolites: A demonstration using deuterated acetaminophen. Biol. Mass Spectrom., 23: 776–783. doi: 10.1002/bms.1200231210
- Issue published online: 11 APR 2005
- Article first published online: 11 APR 2005
- Manuscript Revised: 8 AUG 1994
- Manuscript Received: 21 JUN 1994
The combination of a universal high-performance liquid chromatography/mass spectrometry (HPLC/MS) interface (UI) and the element and isotope-selective capabilities of the chemical reaction interface (CRI) has potential as a comprehensive analysis system for drug conjugates. In this work, we found equal sensitivity for model compounds as their sulfate or glucuronide conjugates. We examined urine and bile samples from Syrian golden hamsters after dosing with (2H4)acetaminophen (D4-APAP), with particular emphasis on the rich range of conjugated metabolites that are known to be produced. Seventeen metabolites were quantified from a single chromatogram of urine; 14 were conjugates. With a combination of authentic standards, selective hydrolysis, and sulfur-selective CRIMS detection, at least partial identification of most of these metabolites was accomplished. The glutathione conjugate of APAP appears the dominant meabolite in bile. The quantitative pattern of APAP metabolism found here is consistent with literature values. It does appear that this HPLC/UI/CRIMS combination has substantial ability to carry out comprehensive metabolite determinations, especially for conjugated species.