间苯三酚颗粒在家兔体内的药动学研究

Pharmacokinetic Study of Phloroglucinol Granules in Rabbits in vivo

目的：建立间苯三酚血药浓度的测定方法，并研究间苯三酚颗粒在家兔体内的药动学特征。方法：取6只健康家兔ig给予间苯三酚颗粒（80mg／kg）溶液，于给药前和给药后O．083、0．17、O．25、O．3、O．33、O．42、0．5、0．75、1、1．5、2、3、4、6h分别自耳动脉采血1．5ml。采用高效液相色谱法检测其血药浓度，色谱柱为WelchromC18＇流动相为乙腈．磷酸盐缓冲液（3．5：96．5），流速为1．0ml／min，柱温为30℃，检测波长为267nm，进样量为20ul，内标为对苯二酚。采用DAS2．1．1药动学软件计算其药动学参数。结果：间苯三酚在0．12～3．0p-g／ml质量浓度范围内与其峰面积与内标峰面积的比值呈良好的线性关系（r=0．9993），提取回收率为86．02％～91．33％，RSD为4．9％～5．3％（，2=3），日内RSD为4．5％～5．6％（n=3），日间RSD为4．9％～5．8％（n=3）；间苯三酚在家兔体内的药动学参数t1/2β、tmax、Cmax、AUC0-6h分别为（1．05±O．16）h、（O．25±O．05）h、（1076．01±19．62）μg／L、（919．02±34．00）μg·h／L。结论：该法专属性强、精密度好，符合血浆样品测定要求，可用于间苯三酚家兔体内的药动学研究。间苯三酚颗粒在家兔体内代谢过程符合一室模型。

OBJECTIVE： To establish the HPLC method to determine the plasma concentration of phloroglucinol granules in rabbits in vivo. METHODS： In total of 1.5 ml ear arterial blood of 6 healthy rabbits was collected before and 0.083, 0.17, 0.25, 0.3, 0.33, 0.42, 0.5, 0.75, 1, 1.5, 2, 3, 4 and 6 h after phloroglucinol granules （80 mg/kg） solution. HPLC was conducted to de- termine the drug concentration with hromatographic column of Welchrom C18 column, mobile phase was acetonitrile-phosphate buf- fer （3.5：96.5） with the flow speed of 1.0 ml/min, column temperature was 30℃, detection wavelength was 267 mn, injection vol- ume was 20μl. The pharmacokinetics parameters were calculated by DAS 2.1.1. RESULTS： There was a good linear relationship between phloroglucinol and the ratio of peak area and internal standard peak area in the range of 0.12-3.0μg/ml （r=0.999 3） ; ex-traction recovery was in the range of 86.02%-91.33%, RSD was in 4.9%-5.3% （n=3）; intra-day RSD was 4.5%-5.6% （n=3）, inter-day RSD was 4.9%-5.8% （n=3）. The pharmacokinetic parameters of phloroglucinol tl/2β, tmax,Cmax,AUC0-6 h were （1.05 ± 0.16） h, （0.25 ± 0.05） h, （1 076.01 ± 19.62） μg/L, （919.02±34.00）μg·h/L. CONCLUSIONS： This method has advantages in strong specificity, good precision. It is in line with the requirements of plasma samples determination, which can be used for study- ing the pharmacokinetic of phloroglucinol in rabbits. Phloroglucinol granules consistent with single model in rabbits in vivo metabo- lism process.