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Minor Metabolites (minor + metabolite)
Selected AbstractsInterpreting Urine Drug Tests: Prevalence of Morphine Metabolism to Hydromorphone in Chronic Pain Patients Treated with MorphinePAIN MEDICINE, Issue 7 2008Ajay D. Wasan MD ABSTRACT Objective., Pain medicine practitioners frequently use urine drug testing (UDT) to monitor adherence to opioid therapy. It can be difficult to interpret a result as normal or abnormal in relation to which opioid compounds are expected to be found in the urine. We investigated whether hydromorphone may be a metabolite of morphine normally appearing in UDT of patients prescribed morphine. Design., This is a retrospective case-control study of urine toxicology results in pain patients taking only morphine. Inclusion criteria included urine results positive for morphine only (controls) or morphine and hydromorphone (cases). Demographic and medical history variables, and any history of aberrant drug behavior were recorded and related to the presence or absence of hydromorphone in the urine. Results., Hydromorphone was present in 21 of 32 cases (66%), none of whom had a history of aberrant drug behavior. Positive cases occurred more frequently in women, in those taking higher daily doses of morphine, and in those with higher urine morphine concentrations (P < 0.05). Only morphine urine concentration was a significant predictor of the hydromorphone metabolite in a logistic regression model (P < 0.05). Conclusions., Hydromorphone is likely a minor metabolite of morphine, normally appearing in the UDT of patients taking morphine. This finding assists in determining whether a UDT result is normal or abnormal, and subsequently whether a patient is compliant with opioid therapy. This observation should be confirmed by a prospective study in a controlled environment. Variables such as gender, morphine dose, morphine urine concentration, and genetic determinants of morphine metabolism should be investigated further. [source] Clinical (Nonforensic) Application of Ethyl Glucuronide Measurement: Are We Ready?ALCOHOLISM, Issue 6 2010Peter Jatlow Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are minor metabolites of ethanol. Multiple studies have documented that, depending upon the amount of alcohol consumed, they can be measured in biological fluids for hours to days after the parent compound can no longer be detected. Testing for the presence of EtG, in a manner analogous to urinary drug abuse screening, has largely been restricted to forensic and law enforcement situations. Despite a real need for an objective and possibly quantitative marker of ethanol exposure for use in conjunction with outpatient clinical trials and treatment programs, measurement of these metabolites has seen only limited clinical application. The barriers to more extensive clinical use of EtG/EtS testing, particularly misleading assay results that can occur as a consequence of inadvertent exposure to nonbeverage ethanol-containing substances, are reviewed and put into perspective. Additional information needed to develop guidelines for optimal clinical utilization of EtG/EtS measurements is discussed. [source] Identification of circulatory and excretory metabolites of meisoindigo in rat plasma, urine and feces by high-performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2010Meng Huang Meisoindigo has been a routine therapeutic agent in the clinical treatment of chronic myelogenous leukemia in China since the 1980s. However, information relevant to in vivo metabolism of meisoindigo is absent so far. In this study, in vivo circulatory metabolites of meisoindigo in rat plasma, as well as excretory metabolites in rat urine and feces, were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Integration of multiple reaction monitoring with conventional metabolic profiling methodology was adopted to enable a more sensitive detection of in vivo metabolites. By comparing with the MS/MS spectra and retention times of the in vitro reduced metabolites, the major metabolites in rat plasma were proposed to form from 3,3, double bond reduction, whereas the minor metabolites were formed from reduction followed by N-demethylation, and reduction followed by phenyl mono-oxidation. The major metabolites in the rat urine were proposed to form from reduction followed by phenyl mono-oxidation, and its glucuronide conjugation and sulfate conjugation, whereas the minor metabolites were formed from 3,3, double bond reduction, N-demethylation, reduction followed by N-demethylation, phenyl di-oxidation, phenyl mono-oxidation and its glucuronide conjugation and sulfate conjugation. The major metabolites in the rat feces were proposed to form from reduction followed by phenyl mono-oxidation, whereas the minor metabolites were formed from reduction followed by N-demethylation, and reduction followed by phenyl di-oxidation. The phase I metabolic pathways showed a significant in vitro,in vivo correlation in rat. Copyright © 2010 John Wiley & Sons, Ltd. [source] Metabolism of olaquindox in rat liver microsomes: structural elucidation of metabolites by high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2008Zhaoying Liu Olaquindox (N -(2-hydroxyethyl)-3-methyl-2-quinoxalincarboxamide-1,4-dioxide) is a growth-promoting feed additive for food-producing animals. Its toxicity is closely related to the metabolism. The complete metabolic pathways of olaquindox are not revealed. To improve studies of the metabolism and toxicity of olaquindox, its biotransformation in rat liver microsomes and the structure of its metabolites using high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry (LC/MS-ITTOF) were investigated. When olaquindox was incubated with an NADPH-generating system and rat liver microsomes, ten metabolites (M1,M10) were detected. The structures of these metabolites were identified from mass spectra and comparison of their changes in their accurate molecular masses and fragment ions with those of the parent drug. With the high resolution and good mass accuracy achieved by this technique, the elemental compositions of the metabolites and their fragment ions were exactly determined. The results indicate that the N,,,O group reduction is the main metabolic pathway of olaquindox metabolism in rat liver microsomes, because abundant 1-desolaquindox (M2), 4-desolaquindox (M1) and bisdesoxyolaquindox (M9) were produced during the incubation step. Seven other minor metabolites were revealed which were considered to be hydroxylation metabolites, based on the position of the quinoxaline ring or 3-methyl group and a carboxylic acid derivative on the side chain at position 2 of the quinoxaline ring. Among the identified metabolites, five new hydroxylated metabolites (M3,M7) were found for the first time in rat liver microsomes. This work will conduce to complete clarification of olaquindox metabolism, and improve the in vivo metabolism of olaquindox in food animals. Copyright © 2008 John Wiley & Sons, Ltd. [source] Simultaneous detection of monohydroxybenzo[a]pyrene positional isomers by reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 7 2002Hideki Sasaki A liquid chromatographic (LC) method has been developed for the separation of 11 monohydroxybenzo[a]pyrenes (OH BaPs) positional isomers, and for their detection using electrospray ionization mass spectrometry (ESI-MS). All OH BaPs isomers were separated on an octadecylsilyl (C18)-bonded amorphous organosilica column utilizing gradient elution with acetonitrile,water and triethylamine (TEA) at pH 11.0 and determined by MS, except 2- and 8-OH BaPs which were coeluted. The lower detection limits were in the range from 1.6,µg/L for 12-OH BaP to 12,µg/L for 5-OH BaP without any sample enrichment. The relative standard deviations of area response were in the range from 1.8% (9-OH BaP) to 4.9% (12-OH BaP) except for 9.4% (7-OH BaP). The developed method was successfully applied to incubation mixtures of BaP and CYP1A1/epoxide hydrolase. This method identified 1-, 3- and 9-OH BaPs as the major metabolites, and 2- (and/or 8-) and 12-OH BaPs as the minor metabolites in the incubation mixture. Copyright © 2002 John Wiley & Sons, Ltd. [source] Hydroxylation of the Triterpenoid Nigranoic Acid by the Fungus Gliocladium roseum YMF1.00133CHEMISTRY & BIODIVERSITY, Issue 2 2007Jin-Yan Dong Abstract The ability of the fungus Gliocladium roseum YMF1.00133 to transform the bioactive nigranoic acid (=(24Z)-9,19-cyclo-3,4-secolanosta-4(28),24-diene-3,26-dioic acid) was investigated. Three new products from the co-cultures of nigranoic acid and G.,roseum YMF1.00133 were obtained by employing a combination of Sephadex LH-20 and silica-gel column chromatography. The major metabolite was identified as 15, -hydroxynigranoic acid, and the minor metabolites as 6,,15, -dihydroxynigranoic acid and 7,,15, -dihydroxynigranoic acid by mass spectrometry and NMR spectroscopy. This is the first report of the biotransformation of the A-ring-secocycloartene triterpenoid, nigranoic acid. [source] | |||||||||||||