Capillary electrophoresis contributions to the hydromorphone metabolism in man

Abstract

CE-ESI multistage IT-MS (CE-MS(n), n < or = 4) and computer simulation of fragmentation are demonstrated to be effective tools to detect and identify phase I and phase II metabolites of hydromorphone (HMOR) in human urine. Using the same CE conditions as previously developed for the analysis of urinary oxycodone and its metabolites, HMOR and its phase I metabolites produced by N-demethylation, 6-keto-reduction and N-oxidation and phase II conjugates of HMOR and its metabolites formed with glucuronic acid, glucose, and sulfuric acid could be detected in urine samples of a patient that were collected during a pharmacotherapy episode with daily ingestion of 48 mg of HMOR chloride. The CE-MS(n) data obtained with the HMOR standard, synthesized hydromorphol and hydromorphone-N-oxide, and CYP3A4 in vitro produced norhydromorphone were employed to identify the metabolites. This approach led to the identification of previously unknown HMOR metabolites, including HMOR-3O-glucide and various N-oxides, structures for which no standard compounds or mass spectra library data were available. Furthermore, the separation of alpha- and beta-hydromorphol, the stereoisomers of 6-keto-reduced HMOR, was achieved by CE in the presence of the single isomer heptakis(2,3-diacetyl-6-sulfato)-beta-CD. The obtained data indicate that the urinary excretion of alpha-hydromorphol is larger than that of beta-hydromorphol.

CE at the omics level: Towards systems biology – An update

“…Using another type of MEKC, nitrofuran antibiotics and metabolites have also been analyzed [114]. Similar analyses of other drug metabolites have been reported in the last two years [115][116][117][118][119]. Many of these drugs are enantiomeric in nature.…”

The Metabolism of Opioid Agents and the Clinical Impact of Their Active Metabolites

“…60 These minor metabolites include unconjugated and conjugated dihydromorphine (DHM) and dihydroisomorphine (eg, conjugated dihydroisomorphine-3-glucuronide and dihydroisomorphine-6-glucuronide), as well as hydromorphone-3-sulfate, norhydromorphone, and nordihydroisomorphine. 67,68 Hydromorphone is about 5-fold more potent than morphine at the MOR, whereas DHM and norhydromorphone have the same potency as morphine. 69 H3G and H6G are polar substances eliminated by the kidney and are active metabolites that may contribute to opioid toxic effects.…”

Stereoselective determination of drugs and metabolites in body fluids, tissues and microsomal preparations by capillary electrophoresis (2000–2010)

“…These and other selectors, such as phosphated-␥-CD (PH-␥-CD) [94,106,126], carboxymethyl-␤-CD (CM-␤-CD) or carboxymethyl-␥-CD (CM-␥-CD) [75,76,86,87,90,100,102,104,105,117,149], carboxyethyl-␤-CD (CE-␤-CD) [120,121] and sulfobutylether-␤-CD (SBE-␤-CD) [88,[91][92][93]125,128,136,138], are products comprising multiple isomers. Finally, single isomer anionic selectors, such as heptakis (2,3-di-O-acetyl-6-O-sulfo)-␤-cyclodextrin (HDAS-␤-CD) [68,107,119,130,146,148,152], octakis-(2,3-di-Oacetyl-6-O-sulfo)-␥-cyclodextrin (ODAS-␥-CD) [64], and heptakis (2,3-di-O-methyl-6-O-sulfo)-␤-cyclodextrin (HDMS-␤-CD) [130], and the single isomer cationic CD derivative 6-monodeoxy-6-mono(3-hydroxy)propylamino-␤-cyclodextrin (PA-␤-CD) [151], were employed. It is important to realize that in chiral bioanalytical drug monitoring selection of a suitable chiral buffer additive is not only dependent on the drug administrated.…”