高效液相色谱法测定人体地尔硫及其主要代谢物的药物动力学  

The pharmacokinetic studies of diltiazem and its major active metabolites in human by HPLC

作　　者：谈恒山[1] 杨洁[1] 肖克岳 蔡明虹[1] 

机构地区：[1]南京军区南京总医院

出　　处：《中国医院药学杂志》1998年第1期3-5,共3页Chinese Journal of Hospital Pharmacy

摘　　要：用高效液相色谱法（ＨＰＬＣ）测定人血清中地尔硫（ＤＺ）及去乙酰地尔硫（Ｍ１）浓度。以ＳｐｈｅｒｉｓｏｒｂＯＤＳ，５μｍ为层析柱，流动相：甲醇∶乙腈∶水（６０∶１０∶３０），检测波长２３７ｎｍ，以盐酸普罗帕酮为内标。检测范围：ＤＺ为５．４５～２７２．５ｎｇ·ｍｌ－１，Ｍ１为５．８５～２９２．５ｎｇ·ｍｌ－１。最低检测浓度：ＤＺ为２．８７ｎｇ·ｍｌ－１，Ｍ１为１．９９ｎｇ·ｍｌ－１。平均回收率ＤＺ为１０１．８８％，Ｍ１为１０１．７２％，ＲＳＤ均在１２％以内。并对４名受试者口服９０ｍｇ盐酸地尔硫片后，其药时曲线经微机用ＰＫＢＰ－Ｎ１程序拟合，ＤＺ为一房室开放模型，Ｍ１为二房室开放模型，求得ＤＺ和Ｍ１的Ｔ１／２分别为５．６±１．５ｈ和１４±７ｈ。A HPLC method for simultaneous determination of diltiazem(DZ) and its major metabolite desacetyldiltiazem (M1) in human plasma was described using SPHERISORB ODS 5μm analytical column for separation.An aliquot of the aqueous acid phase was chromatographed using methanolacetonitritewater (60∶10∶30) containing 0.08% acetic acid and 0.04% triethylamine as mobile phase.The wavelength used for detection was 237nm.The propafenon was used as the internal standard.The detection ranges were 5.45￣272.5ng·ml-1 for DZ and 5.85￣292.5ng·ml-1 for M1.The methods are highly sensitive with limits of detection at 2.87ng·ml-1 for DZ and 1.99ng·ml-1 for M1 respectively.The recoveries were about 101.88% for DZ and 101.72% for M1 respectively.The RSD values of withinday and betweenday were all lower than 12%.After 4 healthy volunteers received 90mg diltiazem tablets,the time curves of concentration in plasma were fitted by PKBPN1 program.DZ was fitted to a one compartment open model.M1 was fitted to a two compartment open model.The results showed that T1/2 of DZ and M1 were 5.63±1.48h and 14.49±7.08h respectively.

关 键 词：地尔硫ZHUO 代谢物 药物动力学 高效液相色谱法 

分 类 号：R972[医药卫生—药品] R969.1[医药卫生—药学]