The metabolic fate and effects of 2-Bromophenol in male Sprague–Dawley rats

Abstract

2 1. The metabolic fate and urinary excretion of 2-bromophenol, a phenolic metabolite of 3 bromobenzene, was investigated in male Sprague Dawley rats following single intraperitoneal 4 doses at either 0, 100 or 200 mg/kg. 5 2. Urine was collected for seven days and samples analysed using 1 H NMR spectroscopy, 6 inductively coupled plasma (ICP)MS, and UPLC-MS. 7 3. 1 H NMR spectroscopy of the urine samples showed that, at these doses, 2-bromophenol had 8 little effect on endogenous metabolite profiles, supporting histopathology and clinical chemistry 9 data which showed no changes associated with the administration of 2-bromophenol at these 10 doses. 11 4. The use of ICP-MS Provided a means for the selective detection and quantification of 12 bromine-containing species and showed that between 4 and 25% of the dose was excreted via the 13 urine over the 7 days of the study for both the 100 and 200 mg doses respectively. 14 6. The bulk of the excretion of Br-containing material had occurred by 8 hr post administration. 15 UPLC-MS of urine revealed a number of metabolites of 2-bromophenol, with 2-bromophenol 16 glucuronide and 2-bromophenol sulphate identified as the major species. A number of minor 17 hydroxylated metabolites were also detected as their glucuronide, sulphate or O-methyl 18 conjugates. There was no evidence for the production of reactive metabolites.

The Pharmacometabodynamics of Gefitinib after Intravenous Administration to Mice: A Preliminary UPLC–IM–MS Study

“…When the untargeted LC/MS data obtained for each of the time period collections (pre-dose, and 0-3, 3-8, and 8-24 h post-dose) were analyzed in this way, differences were readily observed between control and IV dosed samples by PCA (Figure 1 for positive ESI and Figure S2 for negative ESI). However, despite the clear detection of gefitinib and its metabolites in the urine obtained previously [14], and unlike the situation reported for a number of other compounds, e.g., [30][31][32][33][34], none of the ions associated with them contributed to the observed PCA separation. Thus, as shown in Figure 1A and B for the positive ion data, the removal of all of the previously identified ions associated with gefitinib and its metabolites [14] had no effect on the observed PCA score plot.…”

“…There was also a third group of metabolites where, although detectable in both the 0-3 and 3-8 h collections, the maximum amounts observed were in the 8-24 h urine, typified by the O-desmethyl metabolite M7 (M523595). While readily detected using conventional methods, the absence of these compounds as discriminating features in the PCA analysis is more disappointing when compared with some earlier work, e.g., [23,[30][31][32][33][34]. However, given that the removal of gefitinib-related features from the PCA had no discernible effect on the score plots for PCs 1 and 2, it is unsurprising that the examination of the data confirmed that none of the top 100 discriminating ions were gefitinib-related.…”

“…However, these early studies were often associated with relatively high dose drugs (e.g., paracetamol (acetaminophen) [26,27] or oxpentifylline [28]) or toxicological investigations, where high doses were employed to achieve a toxic effect [29]. Developments in chromatographic analysis and mass spectrometry, together with the application of IM spectrometry, have provided new and efficient methods to investigate the effect of drugs on the endogenous metabolome, and to correlate these with drug/metabolite exposure (e.g., see [30][31][32][33][34]).…”

“…This probably reflects the combination of the major route of excretion being via the feces and the low dose of gefitinib administered. Both factors should be compared with the much higher amounts (often several 100 mg/kg) administered in toxicity studies on, e.g., paracetamol (acetaminophen) [31,33] or 2-bromophenol [33,34], where significant urinary excretion of drug/xenobiotic-related metabolites occurred and contributed to the PCA. Thus, the extensive metabolism of gefitinib, to a large number of metabolites, added to Relative amounts (based on peak response) for gefitinib and selected metabolites in the urine of IV dosed mice for the time points obtained from pooled pre-dose (orange) and 0-3 h (grey), 3-8 (yellow), and 8-24 h (blue) post-dose samples [14].…”

The Environmental Pollutant Bromophenols Interfere With Sulfotransferase That Mediates Endocrine Hormones

“…For example, a previous study has shown that 2,4,6-TBP is a typical substrate of SULTs (16). UPLC-MS analysis of urine samples has identified the sulfate and glucuronide metabolites of 2-BP (17). Therefore, glucuronidation and sulfation are the main elimination pathways of BPs in humans.…”