异喹胍及4-羟异喹胍的HPLC测定  

HPLC ASSAY OF DEBRISOQUINE AND 4-HYDROXYDEBRISOQUINE

作　　者：王宏[1] 徐晓蒙[1] 江文德[1] 诸骏仁 郭璎 Kelvin Chan Keith Arnold 

机构地区：[1]上海医科大学临床药理研究所 [2]中山医院内科 [3]香港中文大学药理学系 [4]罗氏基金会

出　　处：《上海医科大学学报》1990年第4期269-274,共6页Journal of Fudan University(Medical Science)

基　　金：自然科学基金C3870291

摘　　要：本文报道用高效液相色谱法(HPLC)检测尿中异喹胍(Debrisoquine,D)及其在体内的代谢产物4-羟异喹胍(4-hydroxydebrisoquine,HD)排泄量的新方法。并依此计算人体对D的代谢比值,进行志愿者药物羟化代谢的初步研究。胍生(G)为内标,样本用乙酰丙酮衍生化后,经碱化-酸化-碱化溶剂提取。流动相为甲醇:水73:27(v/v),pH3.5,分析柱ODS C_(18),紫外检测波长248nm。尿中D和HD的浓度在0.1～20μg/ml范围内直线相关,r=0.9998,最低检测浓度为0.01μg/ml,四个浓度的方法回收率为97％～103％,天内精密度(CV)1.4％～3.3％,天间精密度(CV)3.0％～5.2％,10例健康志愿者一次口服10 mg D,测算服药后8h内尿中D和HD的含量,代谢比值在0.16—7.95间,均属快代谢型者。A high performance liquid chromatographic (HPLC) method has been deye-lopde for the determination of debrisoquine(D)and its 4-hydroxy metabolite (HD) in urine. Guanoxane (G) was used as an internal standard. D, HD and G were derivatized by acetylacetone, extracted from urine sample, separated on an ODS column with a mobile phase of methanol and water (73:27, v/v). The working pH was 3.5. The detecting UV wavelength was 2-18 nm. The calibration curves of D and HD were both linear for concentrations from 0.1-20μg/ml urine, r= 0.999 8, and their lowest detectable urine concentrations were 10ng/ml, The recoveries were between 97 %- 103% and precision studies of D and HD both within and between days at different levels provided 0V values within 5%. Our preliminary study in volunteers has identified the reliability of this assay method. A small population of 10 native Chinese living in Shanghai were typed as extensive metabolizers, according to the antimode of the metabolite ratio (D/HD) of 12.6.

关 键 词：异喹胍 HPLC 羟化代谢 药代动力学 

分 类 号：R969.1[医药卫生—药理学]