Identification of glucuronide conjugates of ketobemidone and its phase I metabolites in human urine utilizing accurate mass and tandem time‐of‐flight mass spectrometry

Abstract

The glucuronide conjugates of ketobemidone, norketobemidone and hydroxymethoxyketobemidone were identified in human urine post-intravenous administration of Ketogan Novum. The human urine was extracted on a mixed-mode solid-phase micro-column before analysis with liquid chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI-TOF-MS) and tandem MS (MS/MS). Accurate mass and collision-induced dissociation product ion spectra were used for identification of the glucuronide conjugates. Two different TOF mass spectrometers were used and the accurate mass measurements were performed on three separate days with each instrument. The accuracy of the mass measurements was better than 2.1 ppm for two out of three conjugates and the inter-day relative standard deviation was within +/-0.00049%. The MS/MS fragmentation patterns of the conjugates were in accordance with those of the synthetic aglycones and included peaks originating from the [M + H](+) ion of the respective aglycone.

Direct detection of serum psilocin glucuronide by LC/MS and LC/MS/MS: time-courses of total and free (unconjugated) psilocin concentrations in serum specimens of a “magic mushroom” user

“…Liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS are powerful tools for directly detecting highly polar and nonvolatile conjugates; many research groups including our own have reported the detection of conjugates of various compounds using LC/MS and LC/ MS/MS [8][9][10][11][12][13][14][15][16][17][18][19][20]. We reported the identification of urinary psilocin glucuronide (PCG) by LC/MS and LC/MS/MS, and the optimization of its enzymatic hydrolysis conditions for urine, and showed that all PC excreted into urine was in the form of its glucuronide conjugate [15]; in the present study, this line of experiments has been extended to PCG and PC in human serum.…”

Detection and Characterization of Metabolites in Biological Matrices Using Mass Defect Filtering of Liquid Chromatography/High Resolution Mass Spectrometry Data

“…The task of metabolite identification has been greatly facilitated by recent developments in high resolution LC/MS technology [e.g., timeof-flight (ToF) and Fourier transform (FT) mass spectrometers], which allow for the determination of molecular formulae (Corcoran et al, 2000;Zhang et al, 2000;Sundstrom et al, 2002) and product ion formulae (Sleno et al, 2005) with minimal uncertainty. In addition, the specificity of list-dependent acquisition of MS/MS data for expected metabolites is improved (Castro-Perez et al, 2002).…”

Post-acquisition data processing for the screening of transformation products of different organic contaminants. Two-year monitoring of river water using LC-ESI-QTOF-MS and GCxGC-EI-TOF-MS

“…TOF technology uses high sensitivity in full-scan MS analysis along with enhanced selectivity due to the higher resolution and mass accuracy measurement. Hybrid Q-TOF analysers allow the determination of the chemical formula of precursor and product ions (Corcoran et al 2000;Zhang et al 2000;Sundstrom et al 2002;Sleno et al 2005), and they are being employed as one of the major LC-MS platforms for characterizing unknowns, such as TPs (Gómez-Ramos et al 2011).…”