Directly coupled liquid chromatography with inductively coupled plasma mass spectrometry and orthogonal acceleration time-of-flight mass spectrometryfor the identification of drug metabolites in urine: application to diclofenac using chlorine and sulfur detection

We report the application of high-performance liquid chromatography (HPLC) linked to inductively coupled plasma mass spectrometry (ICPMS) and orthogon al acceleration time-of-flight mass spectrometry (oa-TOFMS) for the identif ication of phase I and II urinary metabolites of diclofenac, The metabolite s were separated by reversed-phase HPLC monitored with a UV diode array det ector (UV-DAD) after which 90% of the eluent was directed to an ICPMS sourc e, with the remainder going to an oa-TOF mass spectrometer, Compounds conta ining Cl-35, Cl-37 and S-32 were detected specifically using ICPMS and iden tified by oa-TOFMS, The metabolites detected and identified in this way inc luded 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 dire ct biofluid analysis. Copyright (C) 2001 John Wiley & Sons, Ltd.