Premium
Directly coupled liquid chromatography with inductively coupled plasma mass spectrometry and orthogonal acceleration time‐of‐flight mass spectrometry for the identification of drug metabolites in urine: application to diclofenac using chlorine and sulfur detection
Author(s) -
Corcoran Olivia,
Nicholson Jeremy K.,
Lenz Eva M.,
AbouShakra Fadi,
CastroPerez Jose,
Sage Ashley B.,
Wilson Ian D.
Publication year - 2000
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/1097-0231(20001230)14:24<2377::aid-rcm176>3.0.co;2-5
Subject(s) - chemistry , chromatography , mass spectrometry , metabolite , high performance liquid chromatography , glucuronide , time of flight mass spectrometry , inductively coupled plasma mass spectrometry , ion , organic chemistry , biochemistry , ionization
We report the application of high‐performance liquid chromatography (HPLC) linked to inductively coupled plasma mass spectrometry (ICPMS) and orthogonal acceleration time‐of‐flight mass spectrometry (oa‐TOFMS) for the identification of phase I and II urinary metabolites of diclofenac. The metabolites were separated by reversed‐phase HPLC monitored with a UV diode array detector (UV‐DAD) after which 90% of the eluent was directed to an ICPMS source, with the remainder going to an oa‐TOF mass spectrometer. Compounds containing 35 Cl, 37 Cl and 32 S were detected specifically using ICPMS and identified by oa‐TOFMS. The metabolites detected and identified in this way included glucuronic acid and sulfate conjugates, mono‐ and dihydroxylated and free diclofenac. In addition a previously unreported in vivo metabolite, an N ‐acetylcysteinyl conjugate of diclofenac, was also characterised. This is the first application of the combination of HPLC/UV‐DAD/ICPMS/oa‐TOFMS for the investigation of the metabolic fate of chlorinated xenobiotics by direct biofluid analysis. Copyright © 2001 John Wiley & Sons, Ltd.