Metabolite fractionating urinary

Five years ago both groups began using a multistep procedure for fractionating urinary THC metabolites according to their polarities and acidities utilizing manipulations of solvents and/or pH as seen in Figure 1 (1). This scheme can quantitatively extract all of... 

Brooks LR et al., Mutagenicity of HPLC-fractionated urinary metabolites from... 

HydroxyNPYR [ ] has been identified as a urinary metabolite of NPYR in the rat (up to 1% of the dose), but was not detected when NPYR was incubated with subcellular fractions from rat liver and lung (13, 20). It has been proposed that further metabolism of leads to dimethy 1 amine, [ ], another urinary metabolite of NPYR, 2-Pyrrolidinone [3 ] has also been detected in the urine of rats treated with NPYR. Its origin has not been conclusively established, but it may form from pyrrol id inone-2-oxime (i6). 

Like imines, some oximes are known to undergo metabolic hydrolysis by a nonenzymatic mechanism. Cyclohexanone oxime (11.69), an intermediate in the synthesis of polycaprolactam or Nylon-6, is a good example with which to begin our discussion. Following administration to male rats by various routes, cyclohexanone oxime undergoes rapid metabolism, and only trace amounts of the parent compound can be recovered in the urine [104], Although cyclohexanone (11.70) represented a small fraction of the urinary metabolites, most of the dose was recovered as glucuronides of cyclohexa-nol (11.71) and of cis- and /ran.v-cyclohexanc-1,2-diol. 

Discussion We gave low dose BZ, since the purpose was primarily to measure the amount of BZ excreted intact in the urine, and to test the reliability and sensitivity of the urinary assay method, developed by Kondritzer Animal studies had indicated that only a small fraction of injected BZ was recoverable from urine. Human excretion results likewise showed the fraction of intact drug in the urine to be quite small with most of the BZ consisting of its metabolites. Clinical measures consisted only of general observation and periodic vital signs. Behavioral changes were mild. (The potency of the BZ used in these early studies was found to be less than 90% of the stated value. We were provided with a purer batch for subsequent studies.)... 

The EDI of phthalates in China, Germany, Taiwan, and US populations are shown in Table 7. The calculation was based on phthalate metabolite (primary and secondary) concentrations, the model of David [137] and the excretion fractions according to various authors [23,28,143,144]. DEHP median values are very close or clearly exceed the TDIs and RfD values (Table 4). The median values for the rest of PAEs are below levels determined to be safe for daily exposures estimated by the US (RfD), the EU and Japan (TDI) (Table 4). However, the upper percentiles of DBP and DEHP urinary metabolite concentrations suggested that for some people, these daily phthalate intakes might be substantially higher than previously assumed and exceed the RfD and TDIs. 

Polarographic methods have been extremely useful for the determination of the urinary excretion of the 1,4-benzodiazepines. An assay that employs selective solvent extraction and acid hydrolysis of diazepam and its major metabolites, iV-desmethyldiazepam and oxazepam, to their respective benzophe-nones has been employed to measure the urinary excretion of diazepam [183]. A pulse polarographic assay has been reported that will measure the urinary excretion of bromazepam following a single 12-mg dose [184]. The assay employs selective extraction of bromazepam and the 2-amino-5-bromobenzoyl-pyridine metabolite from the deconjugated metabolites, 3-hydroxybromazepam and 2-amino-3-hydroxy-5-bromobenzoylpyridine, into separate diethyl ether fractions. The residues of the respective extracts are dissolved in phosphate buffer (pH 5.4) and analyzed by pulse polarography, which yields two distinct... 

If CBN is formed in vivo, the appearance of oxygenated CBN metabolites as excretion products would be expected and this has proven to be the cast. Quite independently, Ben-Zvi et al. (23) has identified CBN-7-oic as a sizable fraction of the urinary monkey metabolites of A1-THC. It is, of course, possible that this metabolite could arise by a route not involving... 

The 215nm chromatograms of the pre- and post-drug Eli ether extracts (see Figure 1) equivalent to 2.5mg creatinine are shown in Figure 5. The Eli extract is of interest because of recent work by Greene (this volume) in which the ratio of bound to unbound urinary A9-THC-11 -oic acid, the major known THC metabolite in humans, was proposed to be a function of time after dose. As described in the experimental section, this acid partitions into the Eli fraction. 

At doses of <15 mg/kg for 1 day, >90% of the administered dose was excreted in the urine of both species. There was a linear relationship for the excretion of urinary metabolites up to 15 mg/kg above that level, there was an increased amount of 14C eliminated in the expired air. Mice and rats excreted equal amounts up to 50 mg/kg above this level, metabolism apparently became saturated in mice. In rats, 50% of the 150 mg/kg dose of 14C was eliminated in the expired air in mice, 69% of the 150 mg/kg dose of 14C was eliminated in expired air (Sabourin et al. 1987). The label recovered during exhalation was largely in the form of unmetabolized benzene, suggesting that saturation of the metabolic pathways had occurred. Dose also affected the metabolite profile in the urine. At low doses, a greater fraction of the benzene was converted to putative toxic metabolites than at high doses, as reflected in urinary metabolites. 

The oxazophosphorine cyclophosphamide is initially oxidized to active and inactive metabolites which are secreted by the kidney [72, 73, 74, 75]. The 24 hour urinary excrehon of intact parent compound and alkylahng achvity is respectively 1-14% and 7-17% [76]. The fraction of cyclophosphamide and metabolites excreted in the urine is high and unchanged in patients with renal failure [77]. 

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