Quinidine oxidative metabolism. Identification and biosynthesis of quinidine 10,11-dihydrodiol stereoisomers.
The isocratic reversed phase high performance liquid chromatographic method proposed for quinidine metabolic studies facilitates particularly the separation of 10(R) and (S) isomers of quinidine 10,11-dihydrodiols. The finding of each of these forms following a new synthetic pathway allows us to identify and quantify them in biological fluids. These two isomers have especially been observed in rat bile and hepatocyte secretions. The metabolic inducing effect of phenobarbital on the oxidative metabolism of quinidine is verified in rat isolated hepatocytes. Simultaneous secretion of the two dihydrodiols is also verified in human urine by a gas chromatography/mass spectrometry procedure.
Leroyer
R
R
Pharmacie Centrale, Centre Hospitalier Régional et Universitaire, Caen, France.
Varoquaux
O
O
Advenier
C
C
Pays
M
M
D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides / Q000032:analysis / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010634:Phenobarbital / Q000494:pharmacology; D011802:Quinidine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D011803:Quinine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D003497:Cyclic N-Oxides; C013569:3-hydroxyquinidine; C029819:6'-hydroxycinchonidine; C045112:quinidine-N-oxide; C029822:quinine-10,11-dihydrodiol; D011803:Quinine; D011802:Quinidine; D010634:Phenobarbital