RP-HPLC法测定小鼠各组织中阿糖胞苷及阿糖尿苷浓度

Determination of Cytarabine and Uracil Arabinoside in Tissues of Rats by RP-HPLC

目的:建立在血浆、脑脊液和睾丸组织中同时测定阿糖胞苷及其代谢物阿糖尿苷浓度的反相高效液相色谱法并进行小鼠体检内测定波量长分为析28。0 n方m法,柱:色温谱为柱30为℃X,T进er样ra量C18为,流10动μ相L。为将0.0115 m只o小l.鼠L-随1磷机酸分盐成缓A冲、B液、(Cp H3组=,6分.0)别-乙腹腈腔=注9射5∶阿5,糖流胞速苷为105.09、51 m 0L0.0m、2in 0-010,mg·kg-1,30 min后测定小鼠血浆、脑脊液、睾丸组织中的阿糖胞苷及阿糖尿苷浓度。结果:阿糖胞苷、阿糖尿苷检测浓度线性范围分别为0.25～21.74、0.99～86.96 mg·L-(1r>0.998 8),检测限为0.1～0.4 mg·L-1;平均回收率均≥96%,RSD≤7.19%。阿糖胞苷及阿糖尿苷在小鼠血浆、脑脊液和睾丸组织中的药物浓度有显著性差异,低、中剂量给药组只在血浆中检测出阿糖尿苷。结论:所建立的测定方法简单、快速、准确、重复性好,可为临床上阿糖胞苷和阿糖尿苷血药浓度的监测和药动学研究提供参考。

OBJECTIVE： To develop the RP-PHLC method for the determination of cytarabine （Ara-C） and its metabolite uracil arabinoside （Ara-U） in plasma, cerebrospinal fluid and testicular tissue simultaneously, and to analyze the drug concentrations quantitatively. METHODS： The determination was performed on XTerra C18 column with mobile phase consisted of 0.01 mol·L^-1 phosphate buffer （pH=6.0）-acetonitrile （95 ： 5） at flow rate of 0.95 mL·min^-1. The detection wavelength was 280 nm and injection volume was 10 μL. The column temperature was set at 30 ℃. 15 mice were randomly divided into group A, group B and group C. Those groups were given 150 mg·kg ^-1 Ara-C, 1 000 mg·kg^-1Ara-C and 2 000 mg·kg^-1 Ara-C respectively by intraperitoneal injection. 30 minutes later, the concentrations of Ara-C and Ara-U in plasma, cerebrospinal fluid and testicular tissue were determined. RESULTS： The linear range of Ara-C and Ara-U were 0.25-21.74 mg·L^-1 and 0.99-86.96 mg· L^-1 （r〉0.998 8）. The minimum detection limit were 0.1-0.4 mg·L^-1. The average recovery rates were no less than 96% （RSD≤7.19%）. There were significant difference among the concentration of Ara-C and Ara-U in plasma, cerebrospinal fluid and testicular tissue. Ara-C in plasma hadn＇ t been determined in low-dose group and medium-dose group except for Ara-U. CONCLUSIONS： The method is simple, rapid, accurate and reproducible for plasma concentration monitoring and pharmacokinetic study of Ara-C and Ara-U.