Determination of Novel Phase I Metabolite of Febuxostat Followed by In Vitro, In Vivo Pharmacokinetic and In Silico Studies

A selective and fast technique was developed for the determination of phase I metabolites in human liver microsomal preparation using ultra performance liquid chromatography–tandem mass spectrometry. The metabolism of febuxostat was examined using human liver Microsomes (HLMs). The resulting four metabolites (M1-M4) were detected; out of those solely M3 was not reported. The kinetic of M3 formation were calculated at zero to fifty minutes in HLMs. Moreover, a validated method of M3 in rat plasma was developed and with success applied on pharmacokinetic studies. Additionally, in silico metabolic and toxicity studies were carried out to establish the M3 metabolite and toxicity respectively. Furthermore, the in silico toxicity studies showed that M3 is not probably to exhibit toxicity.