Higashi T, Miura K, Kikuchi R, Shimada K, Hiyamizu H, Ooi H, Iwabuchi Y, Hatakeyama S, Kubodera N
Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan.
Steroids. 2000 May;65(5):281-94. doi: 10.1016/s0039-128x(00)00087-8.
The characterization of new conjugated vitamin D metabolites in rat bile was performed using HPLC, liquid chromatography/tandem mass spectrometry combined derivatization, and GC-MS. After the administration of 24,25-dihydroxyvitamin D(3) to rats, 23, 25-dihydroxy-24-oxovitamin D(3) 23-glucuronide, 3-epi-24, 25-dihydroxyvitamin D(3) 24-glucuronide, and 24,25-dihydroxyvitamin D(3) 3-sulfate were obtained as new biliary metabolites together with 24,25-dihydroxyvitamin D(3) 3- and 24-glucuronides. The above metabolites, except 24,25-dihydroxyvitamin D(3) 3-glucuronide, were obtained from rats dosed with 25-hydroxyvitamin D(3). 23, 25-Dihydroxyvitamin D(3) 23-glucuronide was also obtained from the bile of rats administered 25-hydroxyvitamin D(3) in addition to its 3-glucuronide, 25-glucuronide, and 3-sulfate. Thus, it was found that 24,25-dihydroxyvitamin D(3) and 25-hydroxyvitamin D(3) were directly conjugated as glucuronide and sulfate, whereas at the C-23 position, they were hydroxylated and then conjugated. Furthermore, we found that the C-3 epimerization acts as one of the important pathways in vitamin D metabolism.
采用高效液相色谱法（HPLC）、液相色谱/串联质谱联用衍生化法以及气相色谱-质谱联用仪（GC-MS）对大鼠胆汁中新的共轭维生素D代谢产物进行了表征。给大鼠注射24,25-二羟基维生素D3后，获得了23,25-二羟基-24-氧代维生素D3 23-葡萄糖醛酸苷、3-表-24,25-二羟基维生素D3 24-葡萄糖醛酸苷以及24,25-二羟基维生素D3 3-硫酸盐，同时还有24,25-二羟基维生素D3 3-葡萄糖醛酸苷和24-葡萄糖醛酸苷。除24,25-二羟基维生素D3 3-葡萄糖醛酸苷外，上述代谢产物均来自于注射25-羟基维生素D3的大鼠。从注射25-羟基维生素D3的大鼠胆汁中除了获得其3-葡萄糖醛酸苷、25-葡萄糖醛酸苷和3-硫酸盐外，还获得了23,25-二羟基维生素D3 23-葡萄糖醛酸苷。因此，发现24,25-二羟基维生素D3和25-羟基维生素D3直接与葡萄糖醛酸和硫酸盐结合，而在C-23位，它们先被羟基化然后再结合。此外，我们发现C-3差向异构化是维生素D代谢的重要途径之一。
