炎琥宁在大鼠体内血药浓度测定方法及其药动学研究

目的:建立以高效液相色谱(HPLC)法测定大鼠血浆中炎琥宁含量的方法,并对其药动学进行研究。方法:色谱柱为VP-ODS C18 Column(150mm×4.6mm,5μm),流动相为甲醇-1%醋酸-三乙胺(65∶35∶0.02),内标物为安定,流速为1.0mL·min-1,检测波长为251nm,温度为40℃。用甲醇沉淀蛋白后取上清液过0.45μm微孔滤膜进样分析,采用DAS1.0软件进行药动学参数估算。结果:炎琥宁进样浓度分别在0.05～1.0μg·mL-1(r=0.9999)和1.0～10.0μg·mL-1(r=0.9998)范围内与各自峰面积积分值之比呈良好线性关系;平均回收率为90.12%,RSD=0.508%(n=3)。大鼠静脉注射4mg·kg-1炎琥宁后,其tmax、Cmax、t1/2α和AUC0～240分别为(5.03±1.2)min、(1.09±7.5)mg·L-1、(0.95±4.4)min和(18.14±1.1)mg·min·L-1。结论:炎琥宁在大鼠体内的药动学过程符合二室模型。

Determination Method of Plasma Level of Potassium Sodium in Rat and Study on Its Pharmacokinetics

OBJECTIVE： To determine plasma level of Potassium sodium in rat by a reversed phase high performance chromatographic method（RP- HPLC） and to study its pharmaeokinetics.METHODS： The plasma was deproteinized with methanol that contained an internal standard （diazepamum） and was separated.The plasma samples were chromatographed on VP- ODS C18（150 mm × 4.6 mm, 5 μm） column with a mobile phase consisting of methanol - 1% acetic acid- triethylamine （65 ： 35 ： 0.02） and detected at 251 nm.The flow - rate was 1.0 mL · min^- 1 and the column temperature was set at 40 ℃ . After deproteinization of plasma, supernatant was taken to be filtered through 0.45 μm microporous membrane for analysis.The pharmacokinetics parameters were calculated using DAS 1.0 Software. RESULTS： The linear calibration curve of Potassium sodium in plasma at a concentration range from 0.05 to 1.0 μg · ml^-1（r = 0.999 9） and 1.0 to 10.0μg · ml^- 1（ r = 0.999 8）.The average recovery of Potassium sodium was 90.12% （RSD = 0. 508%, n = 3）.The pharmacokinetie parameters of Potassium sodium in rats after iv. at a dose of 4 mg · kg^- 1 were as follows： tmax, Cmax,t1/ 2α and AUC0-240 were 5.03± 1.2 min, 1.09± 7.5 mg · L^-1, （0.95± 4.4） rain and（18.14± 1.1） mg · min· L^- 1, respectively.CONCLUSION： The pharmaeokinetics of Potassium sodium in rats fits the two- compartment model.