Identification of rat faecal, urinary and biliary metabolites of thionorphine, a novel mixed agonist-antagonist analgesic, using liquid chromatography/electrospray ionization tandem mass spectrometry.
The biotransformation of thionorphine (N-cyclopropylmethyl-7alpha-[(s)-1-hydroxy-1-methyl-3-(2thiophene)-propyl]-6,14-endo-ethano tetrahydrooripavine), a new analgesic, was in-vestigated in rats. The results of metabolite analysis by liquid chromatography/electrospray ionization tandem mass spectrometry with positive ion mode, in which a mobile phase of 10 mM ammonium acetate (pH 3.0)/acetonitrile (25/75) was used, suggested that thionorphine is biotransformed to two potentially active metabolites, the N-dealkylated thionorphine (M-I) and the oxidized thionorphine (M-II), and subsequently form conjugates with glucuronic acid of both thionorphine and the metabolites.
Wei
Shu-Xiang
SX
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, People's Republic of China. l_wsx@sina.com
Zhang
Zhen-Qing
ZQ
Wang
Xiao-Ying
XY
Guo
Ji-Fen
JF
D000284:Administration, Oral; D000700:Analgesics / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001659:Biliary Tract / Q000378:metabolism*; D002853:Chromatography, Liquid; D005243:Feces / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization; D013797:Thebaine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D013997:Time Factors
C488461:7-(1-hydroxy-1-methyl-3-(2-thiophene)propyl)-6,14-endoethanotetrahydronorthebaine; D000700:Analgesics; C488460:N-cyclopropylmethyl-7-(1-hydroxy-1-methyl-3-(2-thiophene)propyl)-6,14-endoethanotetrahydrooripavine; D017450:Receptors, Opioid, mu; D013797:Thebaine