In vitro and in vivo glucuronidation of 24,25-dihydroxyvitamin D3.
Glucuronidation of 24,25-dihydroxyvitamin D3 has been investigated in in vitro and in vivo experiments. Three positional isomers of 24,25-dihydroxyvitamin D3 monoglucuronide were synthesized from 24,25-dihydroxyprovitamin D3 derivatives with Koenigs-Knorr reaction and used as standard samples. In the presence of the rat liver microsomal fraction and uridine-5'-diphosphoglucuronic acid, 24,25-dihydroxyvitamin D3 gave 3- and 24-glucuronides as the main products in almost equal amounts, but only a small amount of the corresponding 25-glucuronide was obtained. 24,25-Dihydroxyvitamin D3 monoglucuronide was deconjugated with rat intestine homogenate, which indicated the entero-hepatic circulation of 24,25-dihydroxyvitamin D3. After the administration of 24,25-dihydroxyvitamin D3 to rats, its 3- and 24-glucuronides were identified from the bile as inferred from the in vitro experiment. However, the in vivo glucuronidation occurred at the 24-position in preference to the 3-position, and the corresponding 25-glucuronide was not detected. These glucuronides were identified in comparison with standard samples based on their chromatographic behavior during high-performance liquid chromatography and data obtained from liquid chromatography-electrospray ionization-mass spectrometry, which was helpful in identifying these compounds.
Higashi
T
T
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Japan.
Horike
M
M
Kikuchi
R
R
Shimada
K
K
D015650:24,25-Dihydroxyvitamin D 3 / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D020719:Glucuronides / Q000138:chemical synthesis / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis
D020719:Glucuronides; D015650:24,25-Dihydroxyvitamin D 3