Urinary metabolites, analysis

Estimation of dose from urinary metabolite analysis.59... 

Estimation of dose from urinary metabolite analysis From the analysis of volunteer s urine for 3,5,6-TCP, the amount of absorbed chlorpyrifos was determined for each individual volunteer. Table 5 summarizes the calculated chlorpyrifos dose based on analysis of urine samples. The average chlorpyrifos dose was estimated to be 7.07 pg/kg, 182% of the dose estimated using physical techniques. 

A. Braun is conducting a 13-week dietary study of 1,1,1-trichloroethane in rats and mice (CRISP Database 1992). The study will include hematological and clinical chemistry examinations, sperm morphology and vaginal cytology examinations, and urinary metabolite analysis. 

Figure 3. High pressure liquid chromatographic analysis of the urinary metabolites of 2 C N nitrosonornicotine in the rat after a dose of 300 mg/kg (31), Peaks...

Szirmai M (1995) Total synthesis and analysis of major human urinary metabolites of dl-tetrahydrocannabinol, the principal psychoactive component of Cannabis sativa L. Dissertation, Uppsala University, Sweden... 

Applicators, mixers, loaders, and others who mix, spray, or apply pesticides to crops face potential dermal and/or inhalation exposure when handling bulk quantities of the formulated active ingredients. Although the exposure periods are short and occur only a few times annually, an estimate of this exposure can be obtained by quantifying the excreted polar urinary metabolites. Atrazine is the most studied triazine for potential human exposure purposes, and, therefore, most of the reported methods address the determination of atrazine or atrazine and its metabolites in urine. To a lesser extent, methods are also reported for the analysis of atrazine in blood plasma and serum. 

Parkhurst et al. [79] described a high performance liquid chromatographic method for the simultaneous determination of primaquine and its metabolites from plasma and urine samples, utilizing acetonitrile deproteinization, and direct injection onto a cyano column. Levels of 100 ng/mL per 20 pL injection could be quantitated. Preliminary pharmacokinetic analysis is reported for two human subjects after oral doses of 60 90 mg primaquine diphosphate. Two apparent plasma metabolites and two possible urinary metabolites are also reported. 

A report entitled Chemical Trespass was issued in May 2004 by the Pesticide Action Network (Schafer et al., 2006). It contained detailed analysis of 2000/01 National Health and Nutrition Examination Survey (NHANES) OP urinary metabolite data and used published methods to estimate exposure levels to parent compounds from creatinine corrected urinary metabolite levels. They focused on chlorpyrifos and its metabolite 3,4,6-trichloro-2-pyridinol (TCP), and found that chlorpyrifos exposures for children ages 6-11 and 12-19 exceeded EPA s chronic population-adjusted dose (cPAD) by surprisingly wide margins. Geometric mean TCP levels were 3 to 4.6 times higher than the EPA-estimated safe dose, as shown in Fig. 14.2. The more heavily exposed children received daily doses more than ten times the safe level. 

In the case of sulfur mustard, analysis of low molecular weight urinary metabolites suffers from the same drawback as in the case of anticholinesterases, i.e., these products are rapidly excreted and provide therefore limited retrospectivity. Similarly, the in vivo lifetime of DNA adducts of sulfur mustard are less than those of protein adducts due to repair of DNA damage. 

When male Wistar rats were exposed to -hexane at concentrations up to 3,074 ppm for 8 hours, analysis of urine showed that 2-hexanol was the major metabolite, accounting for about 60-70% of the total metabolites collected over the 48-hour collecting period (Fedtke and Bolt 1987). This is in contrast to humans, in which the major urinary metabolite is 2,5-hexanedione (Perbellini et al. 1981). The amounts of metabolites excreted were linearly dependent on the exposure concentration, up to an exposure of about 300 ppm. 2-Hexanol and 2-hexanone were detected in the first sample (obtained during the 8-hour exposure) excretion of 2,5-hexanedione was delayed and was not detected until 8-16 hours after exposure began. The amount of 2,5-hexanedione detected depended on sample treatment total excreted amounts over 48 hours were approximately 350 g/kg 2,5-hexanedione without acid treatment and 3,000 g/kg with total acid hydrolysis, indicating conversion of 4,5-dihydroxy-2-hexanone with acid treatment. 

We have been interested in analysis of mutagens in urine, (19-21) as have other groups. (22,23) The analysis of the mutagenicity of urine is complicated by several technical problems. Urinary metabolites are usually present in low concentrations and relatively little urine can be added directly to the Salmonella test system because urinary histidine interferes in the test. In addition, urine contains a variety of conju-... 

While the clinical use of MS/MS of hormonal steroids is new, metabolite analysis by gas chromatography (GC)-mass spectrometry (MS) has been available for 40 years, since few immunoassays were developed for urinary analytes. Profile analysis is a very powerful technique and it must be recognized that with few exceptions, all disorders of steroid synthesis and metabolism first had their metabolome defined... 

Two parallel groups of healthy volunteers received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 d in a randomized, double-blind fashion, followed by concomitant selegiline, 10 mg once daily for 4 d. The safety of this drug combination was assessed by measurements of blood pressure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of selegiline, citalopram, and their metabolites. In addition, plasma was obtained to measure prolactin, epinephrine, norepinephrine, and 3,4-dihydroxyphanolglycol (DHPG), the urinary excretion of norepinephrine and 5-hydroindoleacetic acid (5-HIAA), the urinary metabolite of serotonin. 

Lee et al. (1975) also qualitatively studied urinary metabolites of32P-labeled white phosphorus in rats. They used thin-layer chromatography (TLC) at 4 and 24 hours after a single oral dose to show that radioactive urinary metabolites consisted of two classes of compounds. One of the compounds corresponded to inorganic phosphate, the other compound was less polar and suggested an organic phosphate, although the composition of this class of metabolites was not determined. TLC analysis of liver extract also showed two classes of compounds with similar properties. 

Butler MA, Lang NP, Young JF, Caporaso NE, Vineis P, Hayes RB, Teitel CH, Massengill JP, Lawsen MF, Kadlubar FF. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 1992 2 116-127. 

Nakajima M, Yokoi T, Mizutani M, et al. Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites absence of mutation prescribing the phenotype in the CYP1A2 gene. Cancer Epidemiol Biomarkers Prev 1994 3 413-421. 

Urinary organic acid analysis is useful for differentiating isolated carboxylase deficiencies from the biotin-responsive multiple carboxylase deficiencies. P-Hydroxyisovalerate is the most common urinary metabolite observed in isolated P-methylcrotonyl-CoA carboxylase deficiency, biotinidase deficiency, biotin holo-carboxylase synthetase deficiency, and acquired biotin deficiency. In addition to P-hydroxy-isovalerate, elevated concentrations of urinary lactate, methylcitrate, and P-hydroxypropionate are indicative of multiple carboxylase deficiency. 

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