Abstract

An HPLC method with electrospray ionization and ion-trap mass spectral detection (LC-ESI/MSD Ion Trap SL) for determining nibentan metabolites in human blood plasma is described. The proposed method provides simultaneous determination of nibentan and its metabolites in blood plasma. Three metabolites, hydroxylated, de-ethylated, and de-ethylated-hydroxylated, were found in human blood plasma after a single i.v. administration of nibentan (0.125 mg/kg, 1%). De-ethylated nibentan was the longest lived metabolite. The last two metabolites were found in human blood plasma for the first time. The results were verified and all metabolites were identified using LC—MS and LC—MS/MS. The major pharmacokinetic parameters were calculated.

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