小鼠静脉注射色胺酮的体内药物动力学

Pharmacokinetics of Intravenous Tryptanthrin in Mice

目的:建立了一种测定小鼠血浆中色胺酮含量的HPLC-UV方法,深入探讨静注色胺酮在小鼠体内的药物动力学过程。方法:采用C18色谱柱(250mm×4.6mm,5μm),甲醇-水(60∶40)作为流动相,检测波长251nm,流速1.0ml/min,室温。采用结构相似的4(3H)-喹唑酮作为内标,研究昆明小鼠被静脉给药后0.167-12.0h期间的浓度-时间(C-t)曲线,计算药物动力学参数。结果:色胺酮质量浓度在0.2-25.0μg/ml范围内线性关系良好,r=0.999 4。LLOQ为0.2μg/ml,LOD为40.0ng/ml。日内日间精密度RSDs均小于2.93%,平均提取回收率大于86.44%。小鼠被静注80 mg/kg色胺酮后,t1/2β为4.00h,V1为3.83L/kg,CL为2.93L/(h·kg),AUC0-12为27.33μg·h/ml,AUC0-∞为28.20μg·h/ml,AUMC0-∞为50.02μg·h2/ml,MRT0-∞为1.83h。结论:本实验建立的HPLC-UV方法操作简单、方便,结果准确、可靠,适用于含色胺酮血浆样品的分析检测与色胺酮的药物动力学研究。色胺酮毒性低、安全性好,在小鼠体内吸收、代谢过程较慢、体内分布广。

Objective：To establish an HPLC-UV method for determination of tryptanthrin in mice plasma,and then further to investigate pharmacokinetics of intravenous tryptanthrin in mice.Methods：This analysis was performed on an C18column（250 mm×4.6 mm,5μm）with the mobile phase of methanol-water（60∶40）,the detection wavelength 251 nm,the flow rate 1.0ml/min,and room temperature.4（3H）-quinazolinone was applied as internal standard（IS）.C-t curve between 0.167 hand 12.0hafter single tryptanthrin intravenous injection in mice and related pharmacokinetic parameters were both investigated.Results：The linear concentration range of tryptanthrin was 0.2-25.0μg/ml with a correlation coefficient of 0.999 4.LLOQ was 0.2μg/ml,and LOD was 40.0ng/ml.The RSDs of intra-day and inter-day precisions of this methodwere all less than 2.93%,and the average extraction recovery was more than 86.44%.After mice were injected with 80mg/kg tryptanthrin,we found t1/2β4.00 h,V1 3.83L/kg,CL 2.93L/（h·kg）,AUC0-1227.33μg·h/ml,AUC0-∞28.20μg·h/ml,AUMC0-∞50.02μg·h2/ml,MRT0-∞ 1.83 h.Conclusion：This established HPLC-UV method was simple and convenient.The results were correct and reliable,so that it was suitable for determination of plasma tryptanthrin sample and pharmacokinetics of tryptanthrin.Tryptanthrin showed low toxicity and good safety,its absorption and metabolism in mice were slow with wide tissue distribution.