Isolation and Identification of Morphine N-Oxide α- and β-Dihydromorphines, β- or γ-Isomorphine, and Hydroxylated Morphine as Morphine Metabolites in Several Mammalian Species

Yeh, S.Y.; Krebs, H.A.; Gorodetzky, Charles W.

doi:10.1002/jps.2600680205

Cited by 31 publications

(2 citation statements)

References 37 publications

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“…These data indicated that p-OHMA was mostly excreted as its sulfate in human urine. In contrast, Yeh et al (1979) and Kamata et al (2003) reported that morphine and psilocin, both containing the phenolic hydroxyl group, in common with HMMA, were eliminated mainly as its glucuronide. Thus, the conjugation pattern in phase II metabolism should vary mainly depending on the subtle differences in the compound structures.…”

Section: Conjugation Of Hmma In Humansmentioning

confidence: 79%

Urinary excretion of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats

et al. 2008

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The urinary concentrations of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), specifically 4-hydroxy-3-methoxymethamphetamine sulfate (HMMA-Sul) and 4-hydroxy-3-methoxymethamphetamine glucuronide (HMMA-Glu), have been directly measured in both MDMA users and rats by an established liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) procedure. The concentrations of these conjugates in urine from MDMA users (n ¼ 25) ranged from 6.5 to 202 mM (from 1.8 to 55.6 mg ml À1 ) for HMMA-Sul and from 1.3 to 87.0 mM (from 0.5 to 32.3 mg ml À1 ) for HMMA-Glu, and the ratio of HMMA-Sul to HMMA-Glu ranged from 1.6 to 9.9 (3.1 AE 1.8). These results demonstrate that the sulfation is quantitatively more significant than the glucuronidation for HMMA in humans. In rats, in contrast, almost all the conjugated HMMA (>99%) was excreted as the glucuronide. These findings indicate that hydrolysis should be carefully made in urine analysis by gas chromatography (GC) or gas chromatography-mass spectrometry (GC-MS) by using either an acid or an enzyme possessing both sulfatase and -glucuronidase activities. It is concluded that a considerable interspecies variation exists in the conjugation of HMMA between humans and rats.

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Section: Conjugation Of Hmma In Humansmentioning

confidence: 79%

Urinary excretion of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats

et al. 2008

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“…Morphine-3-glucuronide (M-3-G) is a major metabolite of M, 1) while dihydromorphine (DHM) and hydromorphone, also known as dihydromorphinone (DHMO), are urinary metabolites. 2,3) Our group previously purified a nicotinamide adenine dinucleotide (phosphate) [NAD(P)]dependent enzyme from guinea pig cytosol that catalyzes the conversion of M to morphinone (MO). 4) We subsequently developed a method for simultaneous quantitation of M and its metabolites using HPLC and found that MO and its glutathione adduct (MO-GSH), were excreted in the bile of guinea pigs given M (25 mg/kg), whereas the biliary excretions of DHM and DHMO were minimal.…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of Morphinone and Its Glutathione Adduct Derived from Morphine by Anaerobic Gut Microbes in Guinea Pigs

Kumagai

2022

Biological & Pharmaceutical Bulletin

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Morphinone (MO) and its glutathione adduct (MO-GSH) are excreted into bile of guinea pigs after subcutaneous administration of morphine (M). In the present study, we examined metabolites of M in guinea pig feces. Surprisingly, minimal amounts of MO and MO-GSH were excreted into the feces, whereas dihydromorphine (DHM) and dihydromorphinone (DHMO), which are not found in bile of guinea pigs administered M, were detected in the feces. Incubation of MO and MO-GSH with the contents of the large intestine under anaerobic conditions resulted in their conversion into DHMO. These results suggest that MO-GSH undergoes C-S cleavage by gut microbes to form MO, which is anaerobically reduced to DHMO excreted into feces.

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Methodology for the identification of the urinary metabolites of the analgesic-narcotic antagonist, codorphone, by gas chromatography mass spectrometry

Evans

Leeling

Helms

1982

Biol. Mass Spectrom.

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Methodology is presented for the identification of codorphone and its metabolites in urine samples using gas chromatography mass spectrometry. The procedure focuses on the clean-up of biological samples and a derivatization technique suitable for these samples. Sep-Pak C-18 cartridges were employed in the clean-up procedure permitting the biological sample to be derivatized in a relatively small volume of reagents. The derivatization procedure incorporated a one-step trimethylsilyloxime reaction to prevent enol formation while simultaneously derivatizing free hydroxyl groups with the excess trimethylsilylimidazole present in the reaction mixture. This was followed by the addition of BSTFA directly to this reaction mixture to complete derivatization of any metabolites possessing dealkylation of the nitrogen. Using this derivatization scheme, synthetic metabolites were analyzed by gas chromatography mass spectrometry, and their mass spectra were characterized emphasizing the diagnostic fragment ions observed in the spectra. To illustrate the usefulness of this methodology, a urine sample obtained from a dog that had been dosed with codorphone was analyzed by gas chromatography mass spectrometry, and the metabolites were identified by comparison to the mass spectra of the synthetic derivatives.

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Isolation and Identification of Morphine N-Oxide α- and β-Dihydromorphines, β- or γ-Isomorphine, and Hydroxylated Morphine as Morphine Metabolites in Several Mammalian Species

Cited by 31 publications

References 37 publications

Urinary excretion of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats

Urinary excretion of the main metabolites of 3,4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucuronide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats

Biotransformation of Morphinone and Its Glutathione Adduct Derived from Morphine by Anaerobic Gut Microbes in Guinea Pigs

Methodology for the identification of the urinary metabolites of the analgesic-narcotic antagonist, codorphone, by gas chromatography mass spectrometry

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