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氯法拉滨大鼠血药浓度检测及药动学研究

Determination of Clofarabine in rat plasma and the pharmacokinetic research
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摘要 目的:建立氯法拉滨血药浓度HPLC检测法,研究其在大鼠体内的血浆药动学。方法:色谱条件为Agilent ODS Hypersil C18分析柱(150 mm×4.6 mm,5μm),柱温30℃,紫外检测波长263 nm,流动相为乙腈-水(16∶84),乙酸调pH=4.0,流速1.2 mL/min;氯法拉滨30 mg/kg静脉注射,于给药后0.17、0.33、0.5、0.75、1.0、1.5、2.0、4.0、8.0 h取血,测血药浓度。结果:氯法拉滨与血浆组分分离完全,在0.05~20.0μg/mL浓度范围内线性关系良好(线性方程y=21.758x-0.9155,r=0.999910)。氯法拉滨高、中、低三个浓度的回收率为95%~105%,日内、日间精密度均小于10%。氯法拉滨大鼠体内药动学符合二室模型,主要药动学参数为A=14.20±2.45,B=1.81±0.51,CL=(2.91±0.47)L.h-1.kg-1,AUC(0-t)=(10.22±1.88)mg.L-1.h,t1/2β=(2.03±0.16)h。结论:HPLC紫外法简便、可靠,能够满足氯法拉滨血药浓度监测及药动学研究需要;氯法拉滨在大鼠体内药动学符合二室模型,消除半衰期约为2 h。 AIM: To establish an HPLC method for the determination of Clofarabine concentration in the plasma of rats and calculate the pharmacokinetic parameters. METHODS: All the samples were separated on a Agilent ODS Hypersil C18 analytical column(150 mm×4.6 mm,5 μm) by a mobile phase of acetonitrile-water(16∶84).The analytical column temperature was 30 ℃,the ultraviolet detection wavelength was at 263 nm,and the flow rate was 1.2 mL/min.The dosage of 30 mg/kg was used for the intravenous injection of Clofarabine before we took blood from each rat at 0.17,0.33,0.5,0.75,1.0,1.5,2.0,4.0 and 8.0 h post administration.The plasma concentration of Clofarabine was measured by HPLC.RESULTS:The chromatographic peak of Clofarabine was separated completely with the impurities in rat plasma.Good linearity was found over the range of 0.05-20.0 μg/mL for Clofarabine determination(the linear equation was y=21.758x-0.9155,r=0.999910).The recovery of methodology was 95%~105%,the inter-and intra-day precisions were both less than 10%.The concentration time curve of Clofarabine in rat could be fitted to two compartment model,and the major pharmacokinetic parameters were as follows: A=14.20±2.45,B=1.81±0.51,CL =(2.91±0.47) L·h-1·kg-1,AUC(0-t)=(10.22±1.88) mg·L-1·h,t1/2β=(2.03±0.16) h.CONCLUSION: This method is selective and sensitive for Clofarabine determination,and can also be used in pharmacokinetic research.The drug shows us a two-compartment model in rat plasma,and it's half-life in plasma of rats was 2 h.
出处 《中国临床药理学与治疗学》 CAS CSCD 2011年第8期852-855,共4页 Chinese Journal of Clinical Pharmacology and Therapeutics
基金 安徽省教育厅优秀青年人才基金(2010SQRL175)
关键词 氯法拉滨 HPLC 大鼠 药动学 Clofarabine HPLC Rat Pharmacokinetics
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