Structural elucidation of rat biliary metabolites of corynoxeine and their quantification using LC-MS(n).
Structural elucidation of rat biliary metabolites of corynoxeine and their quantification using LC-MS(n).
复制标题
DOI：
10.1002/bmc.3149
复制
发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Wei Wang;Xin-Mei Li;Yaping Chen;M. Hattori
中科院分区：
文献类型：
--
作者：
Wei Wang;Xin-Mei Li;Yaping Chen;M. Hattori
Corynoxeine（COR）是钩藤属植物中4种具有生物活性的氧化吲哚生物碱之一。在这项工作中，口服COR后，在大鼠胆汁中检测到两种I相代谢产物，即11-羟基corynoxeine（M1）和10-羟基corynoxeine（M2），以及两种II相代谢产物，即11-羟基corynoxeine 11-O-β-d-葡萄糖苷酸（M3）和10-羟基corynoxeine 10-O-β-d-葡萄糖苷酸（M4（0.105 mmol/kg），通过优化的高效液相色谱-串联质谱法（LC-MS（n）），电喷雾电离，正离子模式。通过LC-MS（n）、核磁共振、圆二色谱和高分辨率MS光谱确定M1-4的结构。通过LC-MS（n）定量大鼠胆汁中的COR及其代谢产物。COR及其代谢物的LC-MS（n）定量方法在5.0 × 10（-10）至5.0 × 10（-7）m范围内具有线性，决定系数≥0.995。稳定性试验回收率为96.80 ~ 103.10%。准确度范围为91.00 - 105.20%。日内和日间测定的相对标准偏差<5.0%。经口给药后0 - 8 h在大鼠胆汁中检测到0.14%的COR，其中总计97.8%的COR生物转化为M1-4。M1和M2的产率分别为48.1%和49.7%，随后分别以47.2%和43.8%的产率葡萄糖醛酸化为M3和M4。
Corynoxeine (COR) is one of 4 bioactive oxindole alkaloids in Uncaria species. In this work two phase I metabolites, namely 11-hydroxycorynoxeine (M1) and 10-hydroxycorynoxeine (M2), and two phase II metabolites, namely 11-hydroxycorynoxeine 11-O-β-d-glucuronide (M3) and 10-hydroxycorynoxeine 10-O-β-d-glucuronide (M4), were detected in rat bile after oral dose of COR (0.105 mmol/kg), by optimized high-performance liquid chromatography-tandem mass spectrometry (LC-MS(n) ) with electrospray ionization in positive ion mode. Structures of M1-4 were determined by LC-MS(n) , nuclear magnetic resonance, circular dichroism and high-resolution MS spectra. COR and its metabolites in rat bile were quantified by LC-MS(n) . The LC-MS(n) quantification methods for COR and its metabolites yielded a linearity with coefficient of determination ≥0.995 from 5.0 × 10(-10) to 5.0 × 10(-7) m. The recoveries of stability tests varied from 96.80 to 103.10%. Accuracy ranged from 91.00 to 105.20%. Relative standard deviation for intra-day and inter-day assay was <5.0%. After the oral dose 0.14% of COR was detected in rat bile from 0 to 8 h, in which in total 97.8% COR biotransformed into M1-4. M1 and M2 yielded 48.1 and 49.7%, which successively glucuronidated to M3 and M4 at 47.2 and 43.8%, respectively.