氯胺酮及其代谢物去甲氯胺酮在大鼠体液及组织中的检测及分布

目的:建立生物检材中氯胺酮及其代谢物去甲氯胺酮的检测方法,考察氯胺酮和去甲氯胺酮在大鼠体内的分布。方法:用高效液相色谱法(HPLC)检测生物检材中的氯胺酮及去甲氯胺酮;以10 mg·kg-1剂量给大鼠灌胃(ig),分别于给药后10 min,45 min,2 h和8 h处死,测定体液和组织中氯胺酮及去甲氯胺酮的含量。结果:建立起生物检材中氯胺酮及其代谢物去甲氯胺酮的HPLC法。所建方法在0.05-25.0μg.g-1浓度范围内线性关系良好,r2=0.999,萃取回收率大于75%;肝和肾中氯胺酮和去甲氯胺酮含量最高,其次为:脾、尿液、肺、脑、血液、心和肌肉。结论:所建方法准确、灵敏,适用于组织中氯胺酮及其代谢物去甲氯胺酮的分析鉴定;肝和肾可作为毒物分析的组织检材。

DETERMINATION AND DISTRIBUTION OF KETAMINE AND ITS METABOLITE NORKETAMINE IN BIOLOGICAL FLUIDS AND TISSUES OF RATS

Objective:To establish the method for determination of ketamine and its metabolite norketamine in biological material and investigate the distribution of ketamine and norketamine in rats.Methods:The concentrations of ketamine and norketamine in biological samples were analyzed by high-performance liquid chromatography(HPLC).Four groups of rats were fed with 10 mg·kg-1 of ketamine and killed at 10 min,45 min,2 h and 8 h post dose,respectively and determine the concentrations of ketamine and norketamine in biological fluids and tissues.Results:A HPLC method for the determination of ketamine and norketamine in biological samples were established.The method showed satisfactory linearity(r2=0.999) in a linear range from 0.05 to 25.0 μg·g-1.The extraction recovery was over 75%.Ketamine and norketamine concentrations of the administrated groups distributed in a degressive order of liver,kidney,spleen,urine,lung,brain,blood,heart,and muscle.Conclusion:The method is accurate,sensitive and suitable for the determination of ketamine and norketamine in tissues.Liver and kidney can be used as tissue samples for toxicological analysis of ketamine and norketamine.