Mandelic Acid in urine

ETHYL BENZENE Mandelic acid in urine End of shift at end of 1.5 g/g creatinine Ns... 

Determination of mandelic acid in urine has been recommended as a biomaiker of exposure to ethylbenzene. Several methods can be used to determine mandelic acid in urine samples. These include derivatization of the acid and GC analysis (detection limit, 1.0 mg/L) isotachophoresis (detection limit, 0.04 mmol/L) and high-performance liquid chromatography (detection limit, 0.01 mmol/L) (WHO, 1996a). 

The determination of mandelic acid in urine is recommended as a biological exposure test for ethylbenzene. The Biological Exposure Index (BEI) Committee of the American Conference of Governmental Industrial Hygienists recommends a mandelic acid concentration in urine of 1.5 g/g creatinine [about 10 mmol/L] as a BEI for ethylbenzene exposure. BEIs represent the levels of the determinants that are most likely to be observed in biological samples collected from healthy workers exposed by inhalation to air concentrations at the level of the TLV. Urine specimens must be collected during... 

Regarding styrene, the variety of controlled human oral and inhalation studies that relate dose to urinary concentration and the existence of a pharmacokinetic model (Droz and Guillemin 1983) could facilitate interpretation of mandelic acid concentration in urine. A caveat in this regard is that other chemical exposures can produce mandelic acid in urine, such as ethyl benzene, acetophenone, and phenylglycine (ACGIH 1991). Those background sources would be more likely to confound low-level general-population biomarker results than workplace end-of-shift results. 

Carboxyhaemoglobin in blood CO in end-exhaled air N,N-Dimethylformamide (DMF) N-Methylformamide in urine Ethyl benzene Mandelic acid in urine... 

A New Gas Chromatographic Method for Determination of Mandelic Acid in Urine... 

Several examples of the applications of polarography in these fields have been already mentioned in Chapters VI and VII, viz. determinations of benzene, toluene, naphthalene and phenols in the atmosphere, breath, blood or urine, of amino acids (with particular interest to tyrosine, tryptophane, phenylalanine, histidine and histamine), of ketoacids, ketosteroids, carbon disulphide in air and blood, ethanol, acetoin, sugars and morphine in blood, of lactic acid, mandelic acid in bile and urine, adrenaline and thyroxine in iodinated proteins and last, but not least, of thiol compounds, both soluble and bound in biological materials. A few further examples will be given here. 

In environmental applications, rosmarinic acid and gallic acids in fermentation liquors (193), and humic acid in river water (194) have been investigated. The occurrence of hippuric, mandelic and phenylglyoxylic acids in urine has been studied (195). 

Methenamine mandelate is a salt of mandelic acid and methenamine and both of these possess property of urinary antiseptic. It is rapidly absorbed in gastrointestinal tract and excreted unchanged in urine, where it broken down in acidic pH (< 5) of urine and formaldehyde is released, which inhibits most of the bacteria. It is administered with sodium biphosphate, mandelic acid or ascorbic acid to keep the urinary pH below 6. Its use is restricted to chronic, resistant type of UTI. 

Methenamine mandelate is the salt of mandelic acid and methenamine and possesses properties of both of these urinary antiseptics. Methenamine hippurate is the salt of hippuric acid and methenamine. Below pH 5.5, methenamine releases formaldehyde, which is antibacterial. Mandelic acid or hippuric acid taken orally is excreted unchanged in the urine, in which these drugs are bactericidal for some gram-negative bacteria when pH is less than 5.5. 

The pBondapak Ci8 column is preceded by a Ci8 pellicular guard column. Mandelic acid elutes in approximately six minutes. Following the elution of mandelic acid, it is necessary to run a short gradient to 60% methanol/40% 0.05 M potassium hydrogen phosphate (pH 4.5) to remove retained compounds from the column in preparation for the next sample injection. Four or five samples may be processed per hour. The sensitivity of this method is 10 mg mandelic acid per liter of urine. Results of urinary levels of mandelic acid have correlated well with the degree of exposure to styrene. 

Mechanism of action In order to act, methenamine [meth EN a meen] must decompose at an acidic pH of 5.5 or less in the urine, thus producing formaldehyde, which is toxic to most bacteria (Figure 32.5). The reaction is slow, requiring 3 hours to reach 90% decomposition. Methenamine should not be used in patients with indwelling catheters. Bacterial resistance to formaldehyde does not develop. [Note Methenamine is frequently formulated with a weak acid such as mandelic acid, which lowers the pH of the urine thus aiding decomposition of the drug.]... 

Disposition in the Body. Readily absorbed after oral administration. Metabolised by A-dealkylation, reduction, deamination, and A-hydroxylation primarily to active metabolites keto-reduction is stereoselective resulting in the formation of threo-hydroxylated metabolites glucuronide formation also occurs along with the formation of hippuric and mandelic acids. About 80 to 90% of a dose is excreted in the urine the amount excreted in the urine is reduced when the urine is alkaline of the urinary excreted material, A-ethylaminopropiophenone, norephedrine (phenylpropanolamine), and hippuric acid are the main metabolites together with small amounts of unchanged drug, amino-propiophenone, A-diethylnorephedrine, and A-ethylnor-ephedrine. 

Disposition in the Body. Rapidly distributed after intravenous injection. It is metabolised in the liver by hydrolysis and N-dealkylation to inactive metabolites. About 90% of a dose is excreted in the urine as the carboxylic acid derivative, together with mandelic acid and benzoic acid less than 5% is excreted as unchanged drug. 

Disposition in the Body. Mandelic acid is a urinary metabolite of several drugs and toxic chemicals and is also found endogenously in normal urine at concentrations of up to 5 pg/ml. 

Disposition in the Body. Slowly absorbed after oral administration. About 50% of a dose is excreted in the urine as unchanged drug in 48 hours and about 4% as 5-phenyloxazolidine-2,4-dione the remainder is excreted in the urine as conjugated pemoline and unidentified polar metabolites mandelic acid is also a metabolite of pemoline. Less than 1% of a dose is eliminated in the faeces. 

Tetrachlorvinphos is readily absorbed through the gastrointestinal tract following oral exposure. Major metabolites following oral exposure in rats and dogs include desmethyl tetrachlorvinphos, 2,4,5-trichlor-ophenylethandiol glucuronide, and 2,4,5-trichloro-mandelic acid. Metabolism and excretion of radioactive tetrachlorvinphos in rats is rapid and majority of radioactivity appears between 0 and 24 h of exposure in urine and feces. 

Methenamine is an antiinfective agent. In acidic urine, methenamine is hydrolyzed to ammonia and formaldehyde, which is bactericidal to certain bacteria in urine. Acid salts (methenamine mandelate and hippurate) have some nonspecific bacteriostatic activity and help to maintain low nrine pH. It is indicated in suppression or elimination of bacterinria associated with pyelonephritis, cystitis, and other chronic UTls in treatment of infected residual urine, sometimes accompanying nenrologic disease or diabetes. 

Methenamine is absorbed orally, but 10 to 30% decomposes in the gastric juice unless the drug is protected by an enteric coating. Because of the ammonia produced, methenamine is contraindicated in hepatic insufficiency. Excretion in the urine is nearly quantitative. When the urine pH is 6 and the daily urine volume is 1000 to 1500 mL, a daily dose of 2 g will yield a concennation of 18 to 60 pg/mL of formaldehyde this is more than the MIC for most urinary tract pathogens. Various poorly metabolized acids can be nsed to acidify the urine. Low pH alone is bacteriostatic, so acidification serves a double function. The acids commonly used are mandelic acid and hippuric acid (Uerx, Hiprex). 

Methenamine (Hiprex) At low urinary pH, is hydrolyzed to formaldehyde which is bactericidal. Formaldehyde kills Gram-negatives, Gram-positives, and funai. Precipitates in presence of sulfonamides. Ammonia produced is somewhat toxic, particularly to the liver. Decrease dose if hepatotoxicity develODS. PO. Conversion to formaldehyde in urine is enhanced by low pH. The acid salts, hippurate or mandelate, help maintain acidic urine. Is not converted to formaldehvde in serum. 

Epinephrine is ultimately metabolized by COMT and MAO to 3-methoxy-4-hydroxy-mandelic acid (vanillylmandelic acid), which is excreted as the sulfate or glucuronide in the urine (Fig. 44.5). 

The metabolites of cyclandelate are mandelic acid, phenylglyoxylic acid and 3,3,5-trimethylcyclohexanol. These are detectable in the urine of rabbits and humans in less than two hours after oral administration (19,20). The ratio of mandelic acid to phenylglyoxylic acid increases with increased dosage (21). Another metabolic study in humans showed that the maximum blood levels of mandelic acid were reached in 0.5 to 1.5 hours after oral dosing (22). 

Isotachophoresis has already been successfully applied to the analysis of urine of persons exposed to styrene, toluene, and xylene, for the contents of mandelic, phenylglyoxylic, hippuric and methylhippuric acids . For the clinical disgnostic of inborne metabolic disorders of purines and pyrimidines, it has been elaborated permitting the identification of different inborne disorders of the metabolism of these bases by the contents of characteristic metabolites excreted in urine (adenine, uric acid, xanthin, deoxyinosin, deoxyguanosin etc.). 

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