LC-MS/MS法研究1-[1-(6-甲氧基-2-萘基)乙基]-2-(4-硝基苄基)-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐在大鼠体内的代谢产物

采用液相色谱-串联质谱法对大鼠灌胃1-［1-(6-甲氧基-2-萘基)乙基］-2-(4-硝基苄基)-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(编号P91024)后粪便、尿液、胆汁和血浆中的主要代谢产物进行研究。通过比较给药样品和空白样品的全扫描总离子流色谱和选择离子扫描色谱图差别寻找I相代谢产物；根据其一级和二级质谱图，确定I相代谢产物的分子结构。完全提取I相代谢产物后的样品溶液，再用葡糖醛酸酶酶解，得II相结合物的苷元部分，采用与I相代谢产物鉴定同样方法寻找和鉴定II相代谢产物苷元的结构，进而确证II相代谢产物的分子结构。从大鼠粪便中鉴定出P91024的2个I相代谢物，从胆汁中鉴定出1个I相和5个II相代谢产物，从尿液中鉴定出1个I相和3个II相代谢产物，从血浆中鉴定出4个I相和1个II相代谢产物；并分别分析推测出它们的结构。P91024在大鼠体内被代谢转化为多种产物，利用LC-MS/MS可以快速寻找和鉴定。

Metabolites of 1-(1-(6-methoxyl-2-naphthyl)ethyl)-2-(4-nitrobenzyl)-6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline hydrobromide in rat by LC-MS/MS method

To investigate the principal metabolites of 1-(1-(6-methoxyl-2-naphthyl)ethyl)-2-(4-nitrobenzyl)-6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline hydrobromide(code designation: P91024) in rats after ig administration by LC-MS/MS,the phase I metabolites were discovered by comparing the fullscan and SIM chromatograms of the test samples with the corresponding blanks.The structures of phase I metabolites were identified by ESI-MS spectra and the product spectra of the corresponding adduct ions.The phase II metabolites were identified in the test samples after the phase I metabolites were completely removed with solvent extraction and then treated with glucuronidase for enzymolysis of phase II glucuronide conjugates and the hydrolysates.Two phase I metabolites of P91024 were identified in rat feces,one phase I and five phase II in bile,one phase I and three phase II in urine,and four phase I and one phase II in plasma.Their structures were elucidated,separately.P91024 was extensively metabolized in rat.The metabolites can be easily screened and identified by LC-MS/MS method.