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Investigation of drug metabolism using capillary electrophoresis with photodiode array detection and online mass spectrometry equipped with an array detector
Author(s) -
Tomlinson Andy J.,
Benson Linda M.,
Johnson Kenneth L.,
Naylor Stephen
Publication year - 1994
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.1150150110
Subject(s) - chromatography , chemistry , metabolite , mass spectrometry , ammonium acetate , capillary electrophoresis , electrospray ionization , capillary electrophoresis–mass spectrometry , electrospray , acetic acid , high performance liquid chromatography , biochemistry
The application of capillary electrophoresis (CE) with photodiode array detection (DAD) and on‐line CE‐mass spectrometry (CE‐MS) equipped with a position and time resolved (PATRIC tm ) focal plane detector for analysis of both in vitro and in vivo drug metabolism is demonstrated. Separation of metabolites derived from the neuroleptic drug haloperidol, by CE, using a simple, volatile run buffer containing 50 m M ammonium acetate with 10% methanol and 1% acetic acid is reported. The potential utility of CE‐DAD for screening drug metabolite mixtures derived from hepatic microsomal incubations is demonstrated for haloperidal (HAL). Also the potential problems associated with using this technology to screen human urine samples for HAL metabolites is discussed. Furthermore, the usefulness of CE‐MS and CE‐electrospray ionization skimmer collision induced dissociation‐MS (CE‐ESI‐CID‐MS) in identification and structure elucidation of HAL metabolites derived from both a guinea pig hepatic microsomal incubation and urine from a patient treated with 0.5 mg/day of HAL is shown. The utility of such an approach in the general area of clinical pharmacology is also discussed.