论文部分内容阅读
Aim:To investigate the biotransformation of metoprolol,a β_1-cardioselectiveadrenoceptor antagonist,by filamentous fungus,and to compare the parallelsbetween microbial transformation and mammalian metabolism.Methods:Fivestrains of Cunninghamella (C elegans AS 3.156,C elegans AS 3.2028,C echinulataAS 3.2004,C blakesleeana AS 3.153 and AS 3.910) were screened for the ability totransform metoprolol.The metabolites of metoprolol produced by C blakesleeanaAS 3.153 were separated and assayed by liquid chromatography-tandem massspectrometry (LC/MS~n).The major metabolites were isolated by semipreparativeHPLC and the structures were identified by a combination of LC/MS~n and nuclearmagnetic resonance analysis.Results:Metoprolol was transformed to 7metabolites;2 were identified as new metabolites and 5 were known metabolites inmammals.Conclusion:The microbial transformation of metoprolol was similar tothe metabolism in mammals.The fungi belonging to Cunninghamella speciescould be used as complementary models for predicting in vivo metabolism andproducing quantities of metabolite references for drugs like metoprolol.
Aim: To investigate the biotransformation of metoprolol, a β_1-cardioselective adrenoceptor antagonist, and to compare the parallels between microbial transformation and mammalian metabolism. Methods: Fivestrains of Cunninghamella (C elegans AS 3.156, C elegans AS 3.2028, C echinulata AS 3.2004, C blakesleeana AS 3.153 and AS 3.910) were screened for the ability totransform metoprolol. The metabolites of metoprolol produced by C blakesleeana AS 3.153 were separated and assayed by liquid chromatography-tandem mass spectrometry (LC / MS ~ n) .The major metabolites were isolated by semipreparative HPLC and the structures were identified by a combination of LC / MS ~ n and nuclear magnetic resonance analysis. Results: Metoprolol was transformed to 7metabolites; 2 were identified as new metabolites and 5 were known metabolites inmammals.Conclusion: The microbial transformation of metoprolol was similar tothe metabolism in mammals. The fungi belonging to Cunninghamella speciescould be used as compl ementary models for predicting in vivo metabolism andproducing quantities of metabolite references for drugs like metoprolol.