Identification of Talinolol Metabolites in Urine of Man, Dog, Rat and Mouse after Oral Administration by High-Performance Liquid Chromatography-Thermospray Tandem Mass Spectrometry

✍ Scribed by Schupke, Hubert; Hempel, Roland; Eckardt, Rudolf; Kronbach, Thomas

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 706 KB
• Volume: 31
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(199612)31:12<1371::aid-jms433>3.0.co;2-4

✦ Synopsis

A new specific HPLC-TSP-MS/MS assay for identification of b-blocking drug talinolol and its metabolites in urinary samples of man, dog, rat and mouse after single oral administration has been developed. Centrifuged udnes were directly injected into the HPLC-TSP-MS system. Based on thermospray MS/MS studies of 10 reference compounds, several selective CID-MS/MS reactions were found, which were typical of substructure elements of potential phase I metabolites. In this way the differentiation of various stereochemical positions of the hydroxyl group in the cyclohexyl ring moiety of metabolites was possible. Renal metabolic profiles for all investigated species were generated by HPLC-multiple reaction monitoring (MRM). The detected metabolites were characterized by TSP full scan and MS/MS analysis in relation to synthesized reference compounds. The major metabolic pathway in all species results in the hydroxylation of the cyclohexylring moiety of talinolol. In dog urine, a phase I1 metabolite, the 0-glucuronide of talinolol (I) was found. In order to identify this structure, the use of electrospray ionization was also necessary.