NMR and HPLC-NMR spectroscopic studies of futile deacetylation in paracetamol metabolites in rat and man

Journal of Pharmaceutical and Biomedical Analysis
A W NichollsJ K Nicholson

Abstract

HPLC-NMR spectroscopy has been used to investigate the level of deacetylation followed by reacetylation (futile deacetylation) of metabolites of paracetamol detected in human and rat urine. This has been achieved through the synthesis and administration of paracetamol isotopically labeled at the acetyl group with C2H3, 13CH3 and 13CO-13CH3. Using paracetamol-C2H3 it had been shown that in the rat the sulphate metabolite present in the urine shows 10-13% futile deacetylation depending on the dose, whereas for paracetamol-13CO-13CH3 the corresponding value was about 8%. After solid phase extraction, it was also possible to determine the level of futile deacetylation in the glucuronide metabolite using directly-coupled HPLC-NMR. This approach was facilitated by the use of acetonitrile-d3 as an HPLC eluent and the HPLC-NMR analyses showed that the level of futile deacetylation in the sulphate and glucuronide metabolites were equal at about 9%. The glucuronide of paracetamol-C2H3 was the predominant metabolite in man and following separation using HPLC-NMR, the level of futile deacetylation was shown to be 1% for the glucuronide and 2% for the sulphate, these values being equal within experimental error. This work demonstrates the u...Continue Reading

References

Apr 1, 1976·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G E Smith, L A Griffiths
Jun 30, 1983·Toxicology and Applied Pharmacology·J F NewtonJ B Hook
Oct 1, 1993·Pharmacology & Therapeutics·S H Thomas

❮ Previous
Next ❯

Citations

Apr 4, 2000·Journal of Pharmaceutical and Biomedical Analysis·A W NichollsJ K Nicholson
Mar 31, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Angus N R NeddermanDavid Higton
Nov 27, 2010·Drug Metabolism Reviews·Lizi Zhao, Gisèle Pickering
Dec 23, 2016·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Queenie ChanPaul Elliott
Feb 7, 2018·Scientific Reports·Peter R BradshawToby J Athersuch
Jun 13, 2015·The Journal of Pharmacology and Experimental Therapeutics·Kazuhisa MiyakawaRobert A Roth
Dec 31, 1997·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A W NichollsJ K Nicholson
Feb 16, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rebecca DargueIan D Wilson
Nov 25, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·J C LindonI D Wilson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.