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目的 建立测定海马神经细胞内外地西泮、氟硝西泮和劳拉西泮含量的方法,并比较海马神经细胞模型对这3种药物的吸收利用差异.方法 采用HPLC-CAD法测定含量.色谱柱:Capcell C18(250 mmx4.6 mm,5μm),流动相:乙腈-水(44:56),柱温30℃,流速1.0 mL· min-1,CAD检测器,检测波长254 nm,采用外标法定量.结果 3种苯二氮(卓)类药物与培养基及细胞中的其他成分能很好分离.地西泮、氯硝西泮与劳拉西泮分别在质量浓度1.83 ～ 183.16、1.81 ～190.04、1.74 ～173.56 mg·L-1时呈线性关系(r ＞0.999 0),方法平均加样回收率分别为99.99％、100.42％和99.98％.给药培养24 h的海马神经细胞对地西泮、氟硝西泮和劳拉西泮的平均吸收率:正常组分别为45.11％、32.60％和29.73％,模型组分别为31.30％、25.98％和21.81％;平均转化利用率:正常组分别为72.98％、73.16％和74.90％,模型组分别为78.89％、83.04％和85.01％.结论 正常组对3种药物的吸收效率比模型组更高,而模型组对吸收的药物转化利用率比正常组更高.HPLC-CAD法同时测定海马神经细胞内外液中3种苯二氮(卓)药物浓度的方法准确、快速、简便,可为苯二氮(卓)类药物在海马神经细胞内的药物动力学研究提供检测方法.“,”AIM To establish a method for quantitative determination of diazepam,clonazepamand,lorazepam inside and outside of hippocampal neuronal cells,and study the absorption and utilization of the three components in cell model.METHODS The quantitative method of three kinds of benzodiazepines by HPLC-CAD was established.The samples were separated on C18 column(250 mm ×4.6 mm,5 μm) with the mobile phase consisted of acetonitrile-water(44:56),the column temperature was 30℃,the flow rate was 1.0 mL · min-1,the detection wavelength was 254 nm,and the external standard method was used.RESULTS Three benzodiazepines could be well separated from the other components of the culture medium and cells.In the range of 1.83-183.16 mg · L-1 of diazepam,1.81-190.04 mg· L-1 of clonazepam and 1.74-173.56 mg · L-1 of lorazepam respectively,there were in good linear relationship,and the average recovery rate was 99.99％,100.42％ and 99.98％ respectively.The hippocampal neuronal cells were treated by three benzodiazepines for 24 h.The average absorption rate of normal control group was 45.11％,32.60％ and 29.73％,and the average absorption rate of model group was 31.30％,25.98％ and 21.81％ respectively.The average utilization rate of normal control group was 72.98％,73.16％ and 74.90％,and the average utilization rate of model group was 78.89％,83.04％ and 85.01％ respectively.CONCLUSION The absorption of normal control group is higher than model group,while the utilization of model group is higher than normal control group.The method is accurate and sensitive,and can provide a reference for the study of drug dynamics in hippocampal nerve cell.