Investigation of the metabolic fate of 2‐, 3‐ and 4‐bromobenzoic acids in bile‐duct‐cannulated rats by inductively coupled plasma mass spectrometry and high‐performance liquid chromatography/inductively coupled plasma mass spectrometry/electrospray mass spectrometry

Abstract

Inductively coupled plasma mass spectrometry (ICPMS) has been used to determine the rate and routes of excretion of bromine following the intraperitoneal administration (50 mg kg(-1)) of 2-, 3- and 4-bromobenzoic acids to male bile-duct-cannulated rats. Analysis of urine and bile for (79/81)Br using ICPMS showed that all three bromobenzoic acids were rapidly excreted (82-98%) within 48 h of dosing, primarily via the urine. High-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICPMS) was then used to obtain metabolite profiles for bile and urine. These profiles revealed that extensive metabolism had taken place, with the unchanged bromobenzoic acids forming a minor part of the total of compound-related material detected. Concomitant MS studies, supplemented by alkaline hydrolysis, enabled the identification of the major metabolite of all three of the bromobenzoic acids as a glycine conjugate. Ester glucuronide conjugates were also identified, but formed only a small proportion of total.

The metabolism of 4-bromoaniline in the bile-cannulated rat: application of ICPMS (79/81Br), HPLC-ICPMS & HPLC-oaTOFMS

“…As we, and others have shown elsewhere, the presence of an ICP-detectable atom such as bromine (Abou Shakra et al., 2002 ; Marshall et al., 2002 ; Nicholson et al., 2000 , 2001 ; Packert Jensen et al., 2005 ; Smith et al., 2008 ), iodine (Duckett et al., 2003 , 2007 ; Packert Jensen et al., 2004a ), sulphur (Corcoran et al., 2000 ; Gika et al., 2009 ; Packert Jensen et al., 2004b ) and, to a lesser extent chlorine (Corcoran et al., 2000 ; Duckett et al., 2003 , 2006) in a x enobiotic readily allows for the element specific detection and quantification of metabolites. Providing that the atom being measured is not lost through metabolism determining the concentrations of, for example, bromine in samples such as urine and bile is easily accomplished, allowing the ready determination of the time course of excretion of compound-related material.…”

“…We have therefore undertaken further studies in order to obtain a more complete, and quantitative, metabolic profile for 4-bromoaniline, in bile-cannulated rats, with the additional aim of further characterising and identifying the metabolites of the compound. Previously, we have demonstrated the utility of using bromine-specific ICPMS for obtaining quantitative excretion-balance measurements and metabolic profiles for bromine-containing compounds (Packert Jensen et al., 2005 ; Smith et al., 2008 ) on urine and bile, etc. Here quantitative and qualitative profiling of biofluids has been performed using HPLC-ICPMS with bromine-specific detection, while HPLC-oaTOFMS was used for metabolite identification.…”

Application of Mass Spectrometry for Metabolite Identification

“…The LC effluent was split post column; 90% was directed to an ICPMS where bromine-containing metabolites were detected and quantified, and the remaining fraction (10%) was directed to a TOFMS for metabolite identification. The coupling of LC-ICPMS with TOFMS provided the necessary sensitivity and selectivity for both qualitative and quantitative analyses of metabolites without internal standards or administration of radiolabeled drugs [159,160]. However, this approach fails to detect metabolites when the specific element is lost (e.g.…”

13C CP MAS NMR of halogenated (Cl, Br, I) pharmaceuticals at ultrahigh magnetic fields

“…[34] 13 C CP MAS spectra for three Bromobenzoic acids recorded under similar conditions at two magnetic fields, 9.4 and 21.1 T, are compared in Fig. 5.…”