title: [Biotransformation and Stability of Hydrocotarnine and Diazocarbonylhydrocotarnine and -hydrohydrastinine derivatives (author's transl)].
abstract: After oral application of the weakly basic (pKs = 6.18-6.26) and relatively stable (1 at pH = 7.4; t1/2(35 degrees C) = 6.9 h) secondary 1-diazocarbonylhydrocotarnine or -hydrohydrastinine derivatives 1-4 and of hydrocotarnine (6) to rats, a total of 18 metabolites, predominantly isoquinolines of varying degrees of hydrogenation (7-19), were isolated from 48-hour urine specimens. These isoquinolines result from cleavage of the C-1/C-1' bond as well as from oxygenation (11, 15, 17-19), N-dealkylation (13, 15, 17-19) and O-dealkylation (8-12, 18, 19). Among these isoquinolines were some phenolic betaines (8-11) of which 9 is the major metabolite of the cotarnine derivatives. Furthermore, C-1-substituted metabolites as well as metabolites with benzo-1,2-diazaindolizine (23, 24) or benzodiazepine structure (20, 21) were isolated. Also in an aqueous-alkaline or an aqueous-acidic medium, the cleavage of the C-1/C-1' bond as well as the formation of benzodiazepines follows a non-enzymatic pathway as evidenced by stability studies. The structures assigned to the different compounds are supported by high-resolved mass spectra, further spectroscopic studies (UV, IR and  1H-NMR spectra) and, in part, by comparison with authentical material.
mesh_terms: D000818:Animals; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D003979:Diazonium Compounds / Q000378:metabolism; D004355:Drug Stability; D007546:Isoquinolines / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D044005:Tetrahydroisoquinolines
chemical_list: D003979:Diazonium Compounds; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C024594:hydrocotarnine; C024595:hydrastinine
vernacular_title: Biotransformation und Stablilität von Hydrocotarnin und Diazocarbonylhydrocotarnin-bzw.-hydrohydrastininverbindungen.