Acidic metabolites in urine

Although A9-THC-ll-oic acid is not the most abundant acidic metabolite in urine, its peak levels (hundreds of nanograms per ml) make it a much more accessa-ble form of the drug than free A9-THC in plasma. 

The metabolism of aromatic amino acids (phenylalanine and tyrosine) can be studied following the excretion of their characteristic phenolic acid metabolites in urine using chromatographic methods. These apply acids to the investigations of amino acids themselves in diagnostics. 

Use of High-Resolution Open Tubular Glass Capillary Columns to Separate Acidic Metabolites in Urine Clin. Chem. (Wimston-Salem, N. C.)... 

Knights, B.A., Legendre, M., Laseter, J.L. and Storer, J.S. (1975), Use of high-resolution open tubular glass capillary columns to separate acidic metabolites in urine. Clin. Chem., 21,888. 

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. 

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. 

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... 

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... 

Metabolites of biogeiuc amines have also been analyzed by GC-ECD. For the simultaneous analysis of 5-hydroxyindole-3-acetic acid (5-HIAA), homovanillic acid (HVA) and m- and p-hydroxyphenylacetic acid (m-, p-HPAA), (metabolites of 5-HT, DA, and m- and p-tyramine acid respectively) in urine, a simple acidic extraction followed by derivatization with PFPA (derivatizes phenols) and hexafluoroisopropanol (deriva-tizes carboxylic acid groups) has been used (Davis et al., 1982 Baker et al., 1987). 

Tolmetin - Tolmetin metabolites in urine give positive tests for proteinuria using acid precipitation tests (eg, sulfosalicylic acid). 

Pharmacokinetics Peak response occurs in 4-8 wk. The duration of a single dose is about 10 hr. Hydrolyzed to unoprostone free acid form in the cornea. Rapidly eliminated from plasma. Excreted as metabolites in urine. Half-life 14 min. 

Despite the resolving power of TLC-MS-MS, few applications in drug residue analysis have been reported. One application concerns the HPTLC-MS-MS analysis of a number of nonsteroidal anti-inflammatory drugs, including salicylic acid and its glycine conjugate salicylhippuric acid, diclofenac, indomethacin, naproxen, phenacetin, and ibuprofen (67). Another application describes the detection and identification of some of these compounds or their metabolites in urine by TLC-MS-MS (67). 

Mraz and Nohova (1992b) placed 10 volunteers (5 men, 5 women) in atmospheres of 10, 30 and 60 mg/m dimethylformamide for 8 h and measured the metabolites in urine collected for up to five days. In addition, two men and two women were exposed to 30 mg/m for 8 h per day on five consecutive days. The uptake from the respiratory tract was 90% and the various urinary metabolites examined accounted for 49% of the retained dose. The half-lives of excretion and the urinary recoveries of the metabolites were dimethylformamide, 2 h (0.3% of dose) y-hydroxymcthyl-V-mcthylformamide, 4 h (22%) jV-hydroxymethylfonnamide, 7 h (13%) and the mercapturic acid conjugate, A -acet l-.S -(V-mcthylcarbamoyl)cystcinc, 23 h (13%). 

The metabolism of thiophene (100) was first studied in 1886 by Heffter (1886MI10900), who administered it orally to dogs and noted the increased output of ethereal sulfates in urine. This is typical of aromatic hydrocarbons conversion to phenolic products which are excreted in urine as sulfate conjugates. When fed to rabbits, there was no increase in the ethereal sulfate output, but there was some indirect evidence of the presence in urine of dihydrodiols and thienylmercapturic acids (45MI10900). This was confirmed by Bray and coworkers (71MI10906,68BJ(109)11P>, who studied thiophene and benzothiophene metabolism in rabbits and rats. The only identifiable metabolites in urine were the thienylmercapturic acids (101) and (102), which are probably formed via conjugation of the intermediate... 

Lundquist et al. (76) reported a method for the analysis of the metabolite 2-aminothiazoline-4-carboxylic acid (18) in urine using LC with fluorescence detection after conversion to N-carbamylcysteine by heating with alkali. The analyte was concentrated from urine by cation exchange resin and further processed to remove interfering thiols and disulfides. The LOD was rather high at 0.3 xM. 

Carolyn et al. have reported two additional ultraviolet-absorbing metabolites in urine specimens [12]. The drug is partially metabolized in the liver by modification of the piperazinyl group. Oxo-ciprofloxacin and tV-acetyl-ciprofloxacin microbial activities are comparable to norfloxacin, and desethylene-ciprofloxacin is comparable to nalidixic acid for certain organisms. About 40-50% of an oral dose is excreted unchanged in the urine, and 15% as metabolites. Upto 70% of a parental dose may be excreted unchanged, and 10% as metabolites within 24 h [13, 14]. 

A simple detection of mefenamic acid and its metabolites in urine by thin layer chromatography was reported earlier by Demetriou and Osborne [52] (see Section 6.1). 

No analytical methods specifically used for the determination of tetryl in biological fluids and tissues were located. One attempt to develop a method for detecting tetryl in animal tissues using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection was unsuccessful because of suspected metabolism and binding of the parent compound and/or metabolites to macromolecules (Army 1981a). However, methods were located for the detection of the tetryl metabolites, picric acid and picramic acid, in urine and for the analysis of tetryl in hand swabs. Table 6-1 is a summary of methods used to determine tetryl metabolites in urine and tetryl in hand swabs. 

Methods for Determining Biomarkers of Exposure and Effect. Methods have been developed for detecting tetryl metabolites (picric and picramic acid) in urine (Zambrano and Mandovano 1956) and analyzing hand swabs for explosives (Douse 1982 Fine et al. 1984 Lloyd 1983b), including tetryl. The colorimetric assays for tetryl metabolites in urine have been used only in animal studies and lack sensitivity. In addition, they are only semiquantitative, and no data on recovery or precision were provided. Analysis methods for tetryl in hand swabs have been used primarily in forensics and not on workers or the general population. No methods for measuring tetryl or its metabolites in the... 

Several tests can show if you have been exposed to benzene. Some of these tests may be available at your doctor s office. All of these tests are limited in what they can tell you. The test for measuring benzene in your breath must be done shortly after exposure. This test is not very helpful for detecting very low levels of benzene in your body. Benzene can be measured in your blood. However, since benzene disappears rapidly from the blood, measurements may be accurate only for recent exposures. In the body, benzene is converted to products called metabolites. Certain metabolites of benzene, such as phenol, muconic acid, and S-phenyl-N-acetyl cysteine (PhAC) can be measured in the urine. The amount of phenol in urine has been used to check for benzene exposure in workers. The test is useful only when you are exposed to benzene in air at levels of 10 ppm or greater. However, this test must also be done shortly after exposure, and it is not a reliable indicator of how much benzene you have been exposed to, since phenol is present in the urine from other sources (diet, environment). Measurement of muconic acid or PhAC in the urine is a more sensitive and reliable indicator of benzene exposure. The measurement of benzene in blood or of metabolites in urine cannot be used for making predictions about whether you will experience any harmful health effects. Measurement of all parts of the blood and measurement of bone marrow are used to find benzene exposure and its health effects. 

Most vitamin D is excreted in the bile less than 5% is excreted as water-soluble metabolites in urine. Some 2% to 3% of the vitamin D in bUe is cholecalciferol, calcidiol, and calcitriol, but most is a variety of polar metabolites and their glucuronide conjugates. In most tissues, the major pathway for inactivation of calcitriol is by way of 24-hydroxylation to calcitetrol, then onward oxidation byway of the 24-oxo-derivative, 23-hydroxylation, and oxidation to calcitroic acid (see Figure 3.3). In addition, a variety of hydroxylated and other polar metabolites have been identified in bile, and many of these onward oxidation products also undergo glucuronide conjugation in the liver (Reddy and Tserng, 1989). 

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