Quaternary ammonium glucuronide of croconazole in rabbits.
1. A water-soluble croconazole glucuronide was isolated from the urine of rabbits dosed intravenously with croconazole, using XAD-2 column chromatography, reversed-phase RP-8 column chromatography and h.p.l.c. 2. beta-Glucuronidase hydrolysis liberated unchanged croconazole from the glucuronide. 3. Secondary ion mass spectra, i.r. and n.m.r. spectroscopic studies, including two-dimensional n.m.r. techniques (ROESY and HETCOR), showed the metabolite to be a quaternary ammonium glucuronide of croconazole: i.e. a chemical bond exists between a nitrogen, having sp2 type orbital, in the imidazole ring of croconazole and the anomeric carbon of glucuronic acid. 4. The urinary excretion of the glucuronide amounted to 2.8 +/- 0.7% of dose (mean +/- SD, n = 4) in rabbits.
Takeuchi
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Nakano
M
M
Mizojiri
K
K
Iwatani
K
K
Nakagawa
Y
Y
Kikuchi
J
J
Terui
Y
Y
D000818:Animals; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D007093:Imidazoles / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D011817:Rabbits; D013055:Spectrophotometry, Infrared
D005965:Glucuronates; D007093:Imidazoles; C038008:croconazole