大鼠体内环磷酰胺和顺铂联合用药的药代动力学初步研究

 目的　建立双波长高效液相色谱同时测定环磷酰胺和顺铂质量浓度的方法，并研究其在大鼠体内的药代动力学。方法　色谱柱为Hypersil-ODS2，流动相为甲醇-水（80∶20），紫外检测器在254 nm和195 nm检测顺铂和环磷酰胺质量浓度。结果　环磷酰胺保留时间为5.15 min，质量浓度线性范围0.5～10 μg／ml（r＝0.9999），平均回收率为97.4 %相对标准偏差（RSD）<5 %]，检测线0.1 μg／ml（信噪比＞3）；顺铂保留时间为9.26 min，质量浓度线性范围0.1～2.0 μg／ml（r＝0.9998），平均回收率为98.1 %（RSD＜5 %），检测线0.1 μg／ml（信噪比＞3）。结论　该法能有效测定两药浓度，并提供了研究其药代动力学的方法，联合用药使二者消除速度下降，消除半衰期延长，存在交互作用。

Preliminary pharmacokinetics study of CTX combination with DDP in rat

Objective To establish an HPLC method for the simultaneous determination of CTX and DDP and to research their pharmacokinetics in rat. Methods The separation was performed on a Hypersil-CTX. Results Retention time of CTX was 5.15 min. The linearity range of calibration curve was 0.5-10 μg/ml (r =0.9999), the average recovery was 97.4 %(RSD＜5 %). The detection limit was 0.1 μg/ml(S/N＞3). For DDP the retention time was 9.26 min and the linearity range of calibration curve was 0.1-2.0 μg/ml (r =0.9998).The average recovery was 98.1%(RSD＜5 %). The detection limit was 0.1 μg/ml (S/N＞3). Conclusion The method is effective for determination of CTX and DDP. It also provides the method eligible for pharmacokinetics of CTX and DDP. Drug combination make eliminating rate decrease and eliminating half life prolong, have effect on each other.