HPLC-荧光法研究二巯基丁二酸在小鼠体内的组织分布特性  

Tissue Distribution Study of Dimercaptosuccinic Acid in Mice by HPLC-Fluorescence Method

作　　者：刘世军[1] 崔晞[2] 孙克明[1] 刘宪勇[1] 张敏[1] 王岩[1] 

机构地区：[1]武警山东总队医院药剂科,济南市250014 [2]山东大学公共卫生学院卫生检验研究所,济南市250012

出　　处：《中国药房》2011年第5期413-416,共4页China Pharmacy

摘　　要：目的:研究二巯基丁二酸(DMSA)在小鼠体内的组织分布特性。方法:采用高效液相色谱(HPLC)-荧光法。生物样品在加钠)入,巯流速基为衍生1.0化m试L·剂mminB-1B,r柱后温进为行3检0℃测;。荧色光谱检柱测为器AEicx=hr3o5m6Bnomnd、-EAmQ=C45180,流nm动。相取为健甲康醇昆-明水(小4鼠0∶6306,只V,V随,含机四分丁为基6组溴,化1铵组和为乙空酸白组,其余5组为给药组。给药组一次性灌胃给予0.5mL的2.6mg·mL-1DMSA后0.5、2、4、6、12h摘眼球取血及脑、心脏、肺脏、肠、肝脏、脾脏和肾脏,测定DMSA含量。结果:DMSA在各种生物样品中检测浓度线性关系良好,r均大于0.996,在脑和其他样本中定量下限分别为0.025、0.1μg·mL-1,萃取回收率均大于75%,日内、日间RSD均小于15%。小鼠给药后0.5h即在肠、肝脏、心脏及血液中达药物浓度峰值,2h后在其他脏器中达峰值;分布浓度由高到低排序为肾脏>血液>肠>肺脏>肝脏>脾脏>心脏>脑。结论:所建立的分析方法准确性好,专属性强,内源性物质干扰小,可以满足对DMSA在小鼠体内过程的研究。小鼠口服DMSA后迅速吸收、分布及消除,并主要经肾脏、肝脏代谢、排泄。OBJECTIVE： To study the tissue distribution of dimercaptosuccinic acid （DMSA） in mice. METHODS： HPLC with fluorescence method was adopted. The biological samples were treated with sulfhedryl derivatization reagent. The determination was performed on AichromBond-AQ C18 column with mobile phase consisted of methanol-water （40 ∶ 60, V/V, containing tetrabutyl ammonium bromide and sodium acetate） and flow rate of 1.0 mL·min-1. The column temperature was 30 ℃. The fluorescence detector equipped with 356 nm excitation and 450 nm emission filters was used for measurement of peaks. 36 healthy Kunming mice were randomly divided into 6 groups. One group was control group, the other 5 groups for the drug group. Drug group was given 2.6 mg·mL-1 DMSA 0.5 mL via i.g. gtt. The samples of blood, brain, heart, lungs, intestines, liver, spleen and kidney were collected and the DMSA was determined 0.5, 2, 4, 6, 12 h after administration. RESULTS： The good linear range of DMSA had been obtained （r0.996）. The lowest detection limit of brain and other samples were 0.025 μg·mL-1 and 0.1 μg·mL-1. The extraction recovery was more than 75% and the RSD of intra-day and inter-day were less than 15%. The peaks of drug concentration were reached at 0.5 h in intestine, liver, heart and blood, and at 2 h in kidney, lung, spleen and brain after an oral administration of DMSA. The concentration of DMSA in tissues was followed as： kidneybloodintestinelungliverspleenheartbrain. CONCLUSIONS： The method is accurate, specific and reliable with less interference of endogenous substances, and it can be applied to the study of DMSA in mice tissue. After an oral administration, the DMSA is rapidly absorbed, distributed and eliminated. The tissue distribution of DMSA is excreted via kidney and liver.

关 键 词：二巯基丁二酸 小鼠 组织分布 高效液相色谱-荧光法 衍生化 

分 类 号：R979.3[医药卫生—药品] R969[医药卫生—药学]