Exploration of inhibition potential of isoniazid and its metabolites towards CYP2E1 in human liver microsomes through LC-MS/MS analysis

Ankit Balhara,Avinash Kumar,Suryakant Kumar,Dodheri Syed Samiulla,Sanjeev Giri,Saranjit Singh

Journal of Pharmaceutical and Biomedical Analysis（2021）

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Abstract

•First report regarding investigation of inhibition potential of isoniazid and its four major metabolites towards CYP2E1 enzyme.•Fraction unbound in microsomal incubation (fu,mic) studied for all five compounds using equilibrium dialysis assay.•Samples analysed by using HPLC coupled to a MDS API-4000-QTRAP® hybrid triple quadrupole/linear ion trap mass spectrometer.•Analysis of two low molecular weight species viz., acetylhydrazine and hydrazine after derivatization with p-tolualdehyde.•CYP2E1 enzyme was not inhibited by the isoniazid and its metabolites.

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Key words

Isoniazid,CYP2E1,Inhibition,Drug-drug interactions,Metabolites,Microsomal binding

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