Journal of Pharmaceutical Research

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The aim of the study was to develop a microbial model for synthesis of paracetamol metabolite for further pharmacological and toxicological studies. The metabolite of paracetamol in microbial cultures was identified, isolated and confirmed using fermentation techniques, Thin Layer Chromatography (TLC) and High Pressure Liquid Chromatography (HPLC) followed by liquid chromatography/mass spectrometry (LC/MS). Among different organisms screened, Cunninghamella echinulata showed an extra peak at 5.1 min in HPLC compared to its controls indicating formation of a metabolite. The metabolite was further characterized by mass spectrometry and was found to be N-acetyl-p-benzoquinoneimine (NAPQI) which is a toxic metabolite. Cunninghamella echinulata was able to metabolize paracetamol to its toxic metabolite by N-hydroxylation and rearrangement similar to human beings. This study has developed a model to produce toxic metabolites of other similar drugs easily for further toxicological and pharmacological studies.

Keywords

Microbial Model, Metabolism, Paracetamol, N-Hydroxylation, NAPQI.
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