Metabolite in urine

F. Munari and K. Grob, Automated on-line HPLC-HRGC instnimental aspects and application for the determination of heroin metabolites in urine , J. High. Resolut. Chromatogr. Chromatogr. Commun. 11 172-176(1988). 

E. Podehrad, M. Heil, S. Leih, B. Geier, T. Beck, A. Mosandl, A. C. Sewell and H. Bohles, Analytical approach in diagnosis of inherited metabolic diseases maple syrup urine disease (MSUD)-simultaneous analysis of metabolites in urine by enantioselective multidimensional capillary gas chromatography-mass specti ometiy (enantio-MDGC-MS) , 7. High Resolut. Chromatogr. 20 355-362(1997). 

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

Shafik TM, Bradway DE, Enos HR, et al. 1973a. Human exposure to organophosphorus pesticides A modified procedure for the gas-liquid chromatographic analysis of alkylphosphate metabolites in urine. J Agr Food Chem 21 625-629. 

The use of the methods for monitoring metabolites of trichloroethylene in blood and urine is, however, rather limited since the levels of TCA in urine have been found to vary widely, even among individuals with equal exposure (Vesterberg and Astrand 1976). Moreover, exposure to other chlorinated hydrocarbons such as tetrachloroethane, tetrachloroethylene, and 1,1,1-trichloroethane would also be reflected in an increase in urinary excretion of TCA. In addition, there may be sex differences regarding the excretion of trichloroethylene metabolites in urine since one experiment shows that men secrete more trichloroethanol than women (Inoue et al. 1989). The use of the level of trichloroethylene adduction to blood proteins as a quantitative measure of exposure is also possible, although obtaining accurate results may be complicated by the fact that several metabolites of trichloroethylene may also form adducts (Stevens et al. 1992). 

Muller G, Spassovski M, Henschler D. 1972. Trichloroethylene exposure and trichloroethylene metabolites in urine and blood. Arch Toxicol 29 335-340. 

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. 

Irth, H., De Jong, G. J., Brinkman, U. A. Th., and Frei, R. W., Determination of disulfiram and two of its metabolites in urine by reversed-phase liquid chromatography and spectrophotometric detection after post-column com-plexation, /. Chromatogr., 424, 95, 1988. 

Pyrethroid insecticides are rapidly metabolized to their inactive acids and alcohol components, which are excreted primarily in urine. A small portion of the absorbed compounds is excreted unchanged. Occupational exposure to pyrethroid insecticides can be assessed by measuring intact compounds or their metabolites in urine. Biological indicators of internal dose in exposed subjects are reported in Table 7. Due to their rapid metabolism, determination of blood concentrations can only be used to reveal recent high-level exposures. 

Actual exposure of the hands was reduced by approximately 95% and 87% for applicators and harvesters, respectively, wearing gloves. Respiratory exposure did not differ significantly between the two trials and was estimated to contribute approximately 4% to the excreted amount of metabolite in urine. Median IPP excretion was reduced 42% and 38% for applicators and harvesters, respectively. IPP excretion of the harvesters was strongly correlated with... 

Hiep, B.T., Khanh, V., Hung, N.K., Thuillier, A., Gimenez, F. (1998). Determination of the enantiomers of chlorpheniramine and its main monodesmethyl metabolite in urine using achiral-chiral liquid chromatography. J. Chromatogr. B 707, 235-240. 

Koch HM, Rossbach B, Drexler H, Angerer J (2003) Internal exposure of the general population to DEHP and other phthalates - determination of secondary and primary phthalate monoester metabolites in urine. Environ Res 93 177-185... 

Baker et al. [52] reported the use of a colorimetric method for the determination of primaquine metabolites, in urine. 

All 23 children had OP insecticide metabolites in their urine in phase one testing, while levels were below the limit of detection during phase two, following the consumption of mostly organic food for just five days. Once the children were back on their normal, conventional food in phase three, the levels of insecticide metabolites in urine returned to those found in phase one. 

Gut I, Kopecky J, Filip J. 1981. Acrylonitrile-14C metabolism in rats Effect of the route of administration on the elimination of thiocyanate and other radioactive metabolites in urine and feces. J Hyg Epidemiol Microbiol Immunol 25 12-16. 

The LC-MS/MS technique has been used to quantify and identify phenolic compounds. In order to quantify, multiple reaction monitoring (MRM), in which there is a combination of the precursor ion and one of its daughter fragments, is used to characterize a particular compound. This behavior should be as specific as possible in samples with a complex mixture of phenolic compounds. This technique has been largely used to quantify phenolic compound metabolites in urine and plasma (Urpf-Sarda and others 2005, 2007). In this context, LC-ESI-MS/MS with negative mode has been applied for the identification of a variety of phenolic compounds in a cocoa sample (Sanchez-Rabaneda and others 2003 Andres-Lacucva and others 2000). 

Mutations in the gene for adenylosuccinate lyase (ASL), inherited as an autosomal recessive disorder in purine metabolism, are associated with severe mental retardation and autistic behavior, but apparently not self-mutilation [10, 11]. This enzyme catalyzes two distinct reactions in the de novo biosynthesis of purines the cleavages of adenylosuccinate (S-Ado) and succinylaminoimidazole carboxamide ribotide (SAICAR), both of which accumulate in plasma, urine and cerebrospinal fluid of affected individuals [12]. Measurements of these metabolites in urine... 

Kutz, F.W., B.T. Cook, O.D. Carter-Pokras, D. Brody, and R.S. Murphy. 1992. Selected pesticide residues and metabolites in urine from a survey of the U.S. general population. Jour. Toxicol. Environ. Health 37 277-291. 

Main metabolites in urine after 7 months of exposure to 100 mg As/L drinking water were DMA and trimethylarsin oxide (TMAO) with minute amounts of tetramethylarsonium (TMA)... 

Hasunuma, R., T. Ogawa, Y. Fujise, and Y. Kawanashi. 1993. Analysis of selenium metabolites in urine samples of minke whales (Balaenoptera acutorostrata) using ion exchange chromatography. Comp. Biochem. Physiol. 104C 87-89. 

The metabolites and metabolic pathway of a new anticonvulsant drug, sodium valproate, in rats were investigated using carbon-14 labeled sodium valproate. Most of the metabolites in urine and bile were a glucuronide conjugate of valproic acid. Free sodium valproate was as little as one-seventh of the total metabolites. In feces, only free sodium valproate was detected, and the possibility of enterohepatic circulation of sodium valproate was presumed. A part of dosed sodium valproate was excreted in expired air in the form of CO2. This degradative reaction took place in liter mitochondria and required CoA and oxygen. It was stimulated by ATP... 

Kato K. et al., 2005. Determination of 16 phthalate metabolites in urine using automated sample preparation and onhne preconcentration/high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 77 2985. 

In Germany, the Human Biomonitoring Commission of the German Federal Environmental Agency continuously establishes the reference values of pyrethroid metabolites in urine, as there is a need for reference values to characterize the... 

Leng G, Kuhn KH, Idel H (1997) Biological monitoring of pyrethroids in blood and pyrethroid metabolites in urine application and limitation. Sci Total Environ 199 173-181... 

Zlatkis, A., Bertsch, W., Lichtenstein, H.A., Tishbee, A., Shunbo, F., Liebich, H.M., Coscia, A.M. and Fleischer, N. (1973) Profile of volatile metabolites in urine by gas chromatography-mass spectrometry. Anal. Chem. 45, 763-767. 

Approximately 10-20% of -hexane absorbed by inhalation is excreted unchanged in exhaled air the remainder is metabolized. Metabolism takes place via mixed-function oxidase reactions in the liver. In a study in which metabolites were measured in workers exposed to 77-hexane (Perbellini et al. 1981), mean concentrations of 77-hexane metabolites in urine were 2,5-hexanedione, 5.4 mg/L 2,5-dimethylfuran,... 

Fedtke N, Bolt HM. 1986b. Methodological investigations on the determination of -hexane metabolites in urine. Int Arch Occup Environ Health 57 149-158. 

Exposure. Measurement of endrin and its metabolites can be useful indicators of exposure. Since endrin is cleared from the blood rapidly, such measurements are suitable only for recent exposures. Additional studies are needed to determine the usefulness of metabolites in urine as biomarkers of exposure in humans. A quantitative relationship between the urinary concentration of anti-12-hydroxyendrin and the dose of endrin should be clarified. 

Evidence of oral absorption in rats is demonstrated in the studies by Albro and Moore (1974), Oishi (1990), and Poon et al. (1995). Forty-eight hours after a gavage dose of di-w-octylphthalate, metabolites were detected in the urine. The major metabolite (60% of the metabolites in urine) was derived from the monoester (Albro and Moore 1974). The mono- -octylphthalate metabolite was found in the blood and testes of rats from 1-24 hours after oral dosing with peak levels reported at 3 hours (for blood) and 6 hours (for testes) (Oishi 1990). Di-ra-octylphthalate was found in the liver and adipose tissue of rats after they were fed this compound for 13 weeks in dietary concentrations up to 5,000 ppm, indicating its absorption (Poon et al. 1995). Although there are insufficient quantitative data for estimating the oral absorption rate, di-/ -octylphthalate appears to be absorbed readily however, it may have to be converted to mono- -octylphthalate for intestinal absorption to occur (Lake et al. 1977). 

Very limited data were found regarding the measurement of di-w-octylphthalate and its metabolites in biological fluids. Table 6-1 summarizes the methods that are available. Analytical methods were located for measuring di-/ -octylphthalatc and its metabolites in urine, blood, and tissues (Albro and Moore 1974 ... 

The biological applications of NMR include the study of the structure of macromolecules such as proteins and nucleic acids and the study of membranes, and enzymic reactions. Newer methods and instruments have overcome, to a large extent, the technical difficulties encountered with aqueous samples and the analysis of body fluids is possible, permitting the determination of both the content and concentration of many metabolites in urine and plasma. NMR is not a very sensitive technique and it is often necessary to concentrate the sample either by freeze drying and dissolving in a smaller volume cm- by solid phase extraction methods. 

The prediction of retention times in a given eluent from log P has been proposed for aromatic hydrocarbons.19 The log A values of phenols21 and nitrogen-containing compounds22 were also related to their logP, and the calculated log P was used for the qualitative analysis of urinary aromatic acids, i.e. for the identification of metabolites in urine from the differences of log P in reversed-phase liquid chromatography.23,24... 

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