高效液相-质谱联用法对盐酸关附甲素在大鼠尿中代谢物的研究  

STUDY ON THE METABOLITES OF GUANFU BASE A HYDROCHLORIDE IN RAT URINE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPH-MASS SPECTRUM

作　　者：阿基业[1] 王广基[1] 柳晓泉[1] 江丹云[1] 刘静涵[2] 

机构地区：[1]中国药科大学中国药科大学药物代谢研究中心,江苏南京210009 [2]中国药科大学中国药科大学植物化学教研室,江苏南京210009

出　　处：《药学学报》2002年第4期283-287,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 39970 862 ) ;973资助项目 (G19980 5 1119)

摘　　要：目的　研究盐酸关附甲素在大鼠尿中的代谢产物。方法　大鼠iv盐酸关附甲素后收集尿 ,用高效液相 质谱联用方法测定。通过与标准化合物的色谱保留时间、分子离子峰、碎片离子峰对照从而鉴定I相代谢物。通过用葡糖醛酸酶和硫酸酯酶酶解鉴定其水解产物 (苷元 )从而确定II相结合物。结果　大鼠尿中发现I相代谢物关附醇胺和关附壬素 ;尿经过葡糖醛酸酶和硫酸酯酶酶解后 ,产生关附甲素和关附壬素。结论　盐酸关附甲素在大鼠体内可以转化为关附壬素、关附醇胺、关附甲素葡糖醛酸和硫酸结合物、关附壬素葡糖醛酸和硫酸结合物。经过生物转化 ,代谢产物的极性增加 。AIM To study the metabolites of guanfu base A hydrochloride (GFA) in rat urine. METHODS Rat urine was collected after iv injection of GFA. Phase I metabolites were identified by HPLC/MS and by comparison with authentic standards. Phase II conjugates were treated with either glucuronidase or sulfatase in presence or absence of glucuronidase specific inhibitor D saccharic acid β 1,4 lactone. The aglycones were identified by HPLC/MS. RESULTS Phase I metabolites guanfu base I (GFI) and guanfu alcohol amine (AA) were separated and identified in rat urine by comparison with authentic standards. Phase II conjugates, for which no authentic standards were available, GFA glucuronide and sulfate conjugates, GFI glucuronide and sulfate were separated and tentatively identified by hydrolysis with glucuronidase or sulfatase, the aglycones, GFA and GFI, were identified in rat urine. CONCLUSION After iv injection of GFA, GFA is metabolized into GFI, AA, GFA glucuronide and sulfate conjugates, GFI glucuronide and sulfate conjugates in rat urine. The polarity of the metabolites is increased, and the effectiveness of them is lower than the parent drug.

关 键 词：盐酸关附甲素 Ⅰ相代谢物 Ⅱ相结合物 高效液相-质谱联用法 LC/MS 大鼠 尿液 抗心律失常药 

分 类 号：R972.2[医药卫生—药品] R969.1[医药卫生—药学]