Directly-coupled HPLC-NMR spectroscopic studies of metabolism and futile deacetylation of phenacetin in the rat.
The metabolism and futile deacetylation of phenacetin has been investigated in the rat via 1H NMR spectroscopic analysis of urine. Animals were dosed with either phenacetin or phenacetin-C2H3 and urine samples were collected for -24-0 (pre-dosing), 0-8. 8-24, and 24-48 h post-dosing. Drug metabolites of the two compounds were concentrated from the urine using solid-phase extraction prior to the use of directly-coupled HPLC-1H NMR spectroscopy for separation and identification. Following dosing of phenacetin, the metabolites identified were paracetamol glucuronide, paracetamol and N-hydroxyparacetamol, whilst paracetamol and N-hydroxyparacetamol sulphate were identified following dosing of phenacetin-C2H3. Quantitatively the percentage futile deacetylation of phenacetin-C2H3 metabolites was found to be 32% in both paracetamol and N-hydroxyparacetamol sulphate. This study further indicated the importance of futile deacetylation in simple analgesics and the value of directly-coupled HPLC-NMR spectroscopy for the study of this process.
Nicholls
A W
AW
Section of Biological Chemistry, Imperial College of Science, Technology and Medicine, London, UK. a.nicholls@ic.ac.uk
Lindon
J C
JC
Farrant
R D
RD
Shockcor
J P
JP
Wilson
I D
ID
Nicholson
J K
JK
D000082:Acetaminophen / Q000652:urine; D018712:Analgesics, Non-Narcotic / Q000378:metabolism* / Q000652:urine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D010615:Phenacetin / Q000378:metabolism*; D051381:Rats
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D010615:Phenacetin