摘要
目的建立测定多药耐药(multidrug resistance,MDR)逆转剂FG020326在KM小鼠血浆中血药浓度的方法。方法将KM小鼠(20.0~25.1)g随机分组,每组6只,♀♂各半,尾静脉注射,给药量为30mg·kg^-1,分时取血、处理。采用反相色谱柱,应用外标法测定FG020326在KM小鼠血浆中的血药浓度。结果在所建立的方法学下,FG020326的保留时间为7.9min;标准曲线为·↑Y=0.0144X-0.0285(r=0.9998),在162.5~41600μg·L^-1血浆浓度范围内呈良好的线性关系,最低检测浓度40μg·L^-1(S/N=3);在650、2600、20800μg·L^-1低、中、高3个浓度下的绝对回收率为68.66%~84.63%,相对回收率为92.58%~110.88%;日内及日间RSD均小于3.2%(n=5)。在室温及冷冻-解冻试验中,FG020326具有良好的稳定性,RSD分别小于1.3%和6.0%。尾静脉单次给药后,FG020326在体内过程符合二室模型,T1/2α为0.088h,T1/2β为5.33h,AUC0-∝。为14183h·μg·L^-1,Vd为0.37L。结论该方法快速、准确、简便,能够满足FG020326药代动力学研究要求。
Aim To establish a method to determine the concentration of FG020326 in the plasma of KM mice by reverse phase high-performance liquid chromatography. Methods KM mice were used throughout the experiment and their body weights ranged from 20. 0 to 25. 1 g. All of them were distributed randomly to different test groups which each had 6 mice. FG020326 was administered at a dose of 30 mg · kg^-1 via tail vein. The external standard method was used for the quantitation of FG020326. Results Under the condition of HPLC, the retention time of FG020326 was 7. 9 min. The standard curve was ·↑Y = 0. 0144X - 0. 0285 ( r = 0. 9998 ) with a validated quantitation range of 162.5~4 1600μg · L^-1, and the lowest concentration of detection in mice plasma was 40μg · L^-1( S/N = 3 ). At the concentration of 650,2 600,20 800 μg · L^-1, absolute recovery rates were ranged from 68.66% to 84. 63% and relative recovery rates were ranged from 92.58% to 110. 88%. The RSD of the precision within-day and between-day were less than 3.2%. At ambient temperature and four freeze-thaw cycles, FG020326 was stable and the RSD was less than 1.3% and 6.0%, respectively. The concentration-time curve of FG020326 was well fitted to a two-compartment model. T1/2α and T1/2β were 0. 088 h and 5.33 h, respectively. AUC0→∞ was 14 183 h·μg·L^-1 and Vd was 0. 37 L. Conclusion The assay method is shown to be sensitive, suitable and accurate for determination of FG020326 in mice plasma.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第1期131-134,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助课题(No30371659)