Transformation of verapamil by Cunninghamella blakesleeana.
A filamentous fungus, Cunninghamella blakesleeana AS 3.153, was used as a microbial model of mammalian metabolism to transform verapamil, a calcium channel antagonist. The metabolites of verapamil were separated and assayed by the liquid chromatography-ion trap mass spectrometry method. After 96 h of incubation, nearly 93% of the original drug was metabolized to 23 metabolites. Five major metabolites were isolated by semipreparative high-performance liquid chromatography and were identified by proton nuclear magnetic resonance and electrospray mass spectrometry. Other metabolites were characterized according to their chromatographic behavior and mass spectral data. The major metabolic pathways of verapamil transformation by the fungus were N dealkylation, O demethylation, and sulfate conjugation. The phase I metabolites of verapamil (introduction of a functional group) by C. blakesleeana paralleled those in mammals; therefore, C. blakesleeana could be a useful tool for generating the mammalian phase I metabolites of verapamil.
Sun
Lu
L
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Huang
Hai-Hua
HH
Liu
Lei
L
Zhong
Da-Fang
DF
D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000378:metabolism*; D002853:Chromatography, Liquid; D003470:Culture Media; D020093:Cunninghamella / Q000254:growth & development / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D014700:Verapamil / Q000737:chemistry / Q000378:metabolism*
D002121:Calcium Channel Blockers; D003470:Culture Media; D014700:Verapamil