title: Quantitation in gradient high performance liquid chromatography/inductively coupled mass spectrometry investigated using diclofenac and chlorpromazine.
abstract: The use of directly coupled high performance liquid chromatography/inductively coupled plasma mass spectroscopy (HPLC/ICPMS) employing chlorine ((35)Cl/(37)Cl) detection has been investigated with respect to the detection and quantitation of the drugs diclofenac and chlorpromazine. By integration of peak areas in the 'chloratogram' (the chlorine specific HPLC chromatogram), a calibration curve was constructed, from which the concentrations could be determined. Chlorine detected HPLC/ICPMS is quantitative over a wide range of concentrations of pharmaceutical relevance for metabolite detection and the results reproducible (standard deviation +/- 0.43%) over multiple injections. Application of gradient chromatography and variation in the bulk mobile phase physicochemical properties has little effect on the ICPMS detection response for these compounds. This work indicates that the use of HPLC/ICPMS is likely to be quantitatively reliable for metabolism studies for a range of chlorinated xenobiotics.
authors.affiliation: Biological Chemistry, Division of Biomedical Sciences, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Duckett
authors.forename: Nigel J C
authors.initials: NJ
authors.lastname: Bailey
authors.forename: Heather
authors.initials: H
authors.lastname: Walker
authors.forename: Fadi
authors.initials: F
authors.lastname: Abou-Shakra
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis*; D014150:Antipsychotic Agents / Q000032:analysis*; D002723:Chlorobenzoates / Q000737:chemistry; D002746:Chlorpromazine / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000032:analysis*; D013058:Mass Spectrometry; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014150:Antipsychotic Agents; D002723:Chlorobenzoates; D004008:Diclofenac; C073069:2,5-dichlorobenzoic acid; D002746:Chlorpromazine