In vitro metabolism study of Strychnos alkaloids using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry.
In this report, the in vitro metabolism of Strychnos alkaloids was investigated using liquid chromatography/high-resolution mass spectrometry for the first time. Strychnine and brucine were selected as model compounds to determine the universal biotransformations of the Strychnos alkaloids in rat liver microsomes. The incubation mixtures were separated by a bidentate-C18 column, and then analyzed by on-line ion trap/time-of-flight mass spectrometry. With the assistance of mass defect filtering technique, full-scan accurate mass datasets were processed for the discovery of the related metabolites. The structural elucidations of these metabolites were achieved by comparing the changes in accurate molecular masses, calculating chemical component using Formula Predictor software and defining sites of biotransformation based upon accurate MS(n) spectral information. As a result, 31 metabolites were identified, of which 26 metabolites were reported for the first time. These biotransformations included hydroxylation, N-oxidation, epoxidation, methylation, dehydrogenation, de-methoxylation, O-demethylation, as well as hydrolysis reactions.
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, 210009, China.
Ji-Xin
JX
Tian
Can
C
Peng
Lei
L
Xu
Yuan
Y
Tian
Zun-Jian
ZJ
Zhang
D000470:Alkaloids / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013331:Strychnine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D031451:Strychnos / Q000737:chemistry*
D000470:Alkaloids; C083806:brucine; D013331:Strychnine