In-Vitro Synthesis of Drug Metabolites and their Screening/Characterization Using Liquid Chromatography-Mass Spectrometry (LC-MS)

摘要

For Flunixin, aliphatic hydroxylated metabolite and its opened ring intermediate were the most prevalent peaks. The conversion of flunixin to hydroxymethyl flunixin 1a and its opened ring intermediate 1c was around 2-5%. Similarly, for dicoumarol the most predominant metabolites were formed from decarboxylation of dicoumarol 2a (～10%) and formylation lactone ring opening 2b (～8%). In summary, the BMO kit was an effective tool for the rapid in-vitro synthesis of drug metabolites. However, it is not yet known whether the kit provides optimum conditions to mimic biological metabolite production. For example, data obtained showed that the conversion of flunixin to 5-hydroxy flunixin was less than 1%, but numerous in-vivo studies with flunixin have reported 5-hydroxy flunixin as the major metabolite formed in the biological system.