Identification of the metabolites of MX/2/120 in the guinea-pig by high-performance liquid chromatography/thermospray tandem mass spectrometry

Article abstract of DOI:10.1002/jms.1190300220

The metabolism of MX/2/120, a new xanthine derivative endowed with potent and long-lasting antibronchospastic activity, was investigated in guinea-pig urine, plasma and bile after intravenous administration of 12.5 mg kg^-1 by high-performance liquid chromatography/tandem mass spectrometry with thermospray ionization. Following a first series of collisionally activated neutral losses and parent ion scan experiments performed on urine samples, potential quasi-molecular ions of possible metabolites were identified, which were then analysed by collisionally activated fragment ion scans. A side-chain carboxylated, a side-chain hydroxylated and a xanthine-ring demethylated metabolite, along with the unmodified drug, were identified. In urine, MX/2/120 and its hydroxylated metabolite were also present as glucuronic acid conjugates. In plasma and bile, only the unmodified drug was found. The structures of the identified metabolites were then confirmed by comparison with the authentic compounds prepared by synthesis.