Paracetamol, metabolites

More recent immunohistochemical studies using antiparacetamol antibodies have shown that covalent binding of a paracetamol metabolite occurs in the damaged centrilobular regions of human liver after overdoses. 

It has been shown by using NMR spectroscopy in conjunction with isotopelabelling studies that there is a significant degree of deacetylation followed by reacetylation (futile deacetylation) of paracetamol metabolites in vivo in the rat [58]. If this also occurs in humans, then it may help to explain the observed incidence of nephrotoxicity of paracetamol in that the process would result in levels of the potent nephrotoxin 4-aminophenol in vivo. Confirmation of the levels of futile deacetylation in individual metabolites of isotopically labelled paracetamol in man has been achieved by using directly coupled HPLC-NMR... 

Figure 13.2.6 On-flow contour plots (600 MHz) of the (a) CE-NMR, and (b) pressurized CEC-NMR separations of the paracetamol metabolites obtained from a human urine extract A, paracetamol glucoronide B, paracetamol sulfate C, hippuric acid...

Paracetamol metabolites, salicylic acid, and salicylic acid metabolites also elute from this system. Retention times relative to paracetamol for these substances in this system are ... 

Paracetamol, metabolites/urine, plasma HPLCUV Column EPS Cig (250 x 4.6 mm, 5 pm) Mobile phase 0.1 M KH2PO4 isopropanoPTHF (100 1.5 0.1 pH 3.7), adjusted with phosphoric acid (isocratic elution) Detection X = 254 nm Plasma protein precipitation (30 % perchloric acid) Urine 20 times dilution, centrifugation LOQ 0.06 pg/mL (paracetamol) 0.13 pg/mL (metabolites) [40]... 

Paracetamol, metabolites/urine UPLC MS Column ChromSpeed (50 x 4.6 mm, monolithic) Mobile phase Solvent A 0.1 % HCOOH in water Solvent B 0.1 % HCOOH in ACN (gradient elution) Detection MS, ionization ESI Five times dilution [42]... 

M. Godejohann, L.-H. Tseng, U. Braumann, J. Fuchser, M. Spraul, Characterization of a paracetamol metabolite using on-line LCSPE-NMR-MS and a cryogenic NMR probe, J. Chromatogr. A, 1058 (2004) 191. 

Several studies have used NMR spectroscopy to determine the number and identity of drug metabolites in bile. These include the use of NMR spectroscopy to study doxifluridine catabolites in human bile, and C NMR spectroscopy of perfluorinated fatty acids in rat bile and NMR for monitoring the formation of formaldehyde from demethylation of antipyrine. NMR spectroscopy of rat bile has been used to monitor the excretion of paracetamol metabolites. A combination of H and H- - C 2D NMR methods has allowed identification of 4-cyano-A,N-dimethylaniline, cefoperazone and benzyl chloride in rat bile. ... 

The further coupling of HPLC-NMR with mass spectrometry has also been used to analyse drug metabolites in urine for the human excretion of paracetamol metabolites. " This approach has also been used to identify metabolites of substituted anilines in rat urine. ... 

Adriaenssens, P. I., and Prescott, L. F. (1978). High performance liquid chromatographic estimation of paracetamol metabolites in plasma. Br. J. Clin. Pharmacol. 6, 87-88. 

Spraul M, Hofmann M, Lindon JC, Farrant RD, Seddon MJ, Nicholson JK, WUson ID. Evaluation of liquid-chromatography coupled with high-field H NMR spectroscopy for drug metabolite detection and characterization the identification of paracetamol metabolites in urine and bile. NMR Biomed 1994 7 295-303. 

Andersson, D. A. etal, Nat. Commun., 2, 2011, 551. (Paracetamol metabolites activate receptors in spinal cord)... 

However, the small injection volume available to CE (a few nl) means that high sensitivity can only be achieved if concentrations of the analyte in the sample are high. Nevertheless, some results have been reported using CE-NMR and the method has been applied to the identification of paracetamol metabolites in human urine. Finally the application of capillary electrochromatography (CEC) directly coupled to NMR has been explored using the same paracetamol metabolite samples. 

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