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[摘要]
目的 建立测定大鼠血浆中阿糖尿苷的LC-MS/MS方法,用于大鼠尾iv注射用盐酸阿糖胞苷后阿糖尿苷在体内的药动学研究。方法 采用LC-MS/MS法。ACQUITY UPLC BEH C18色谱柱(50 mm×2.1 mm,1.7 μm);流动相:水–乙腈,梯度洗脱;体积流量:0.2 mL/min;柱温:40 ℃;进样量:5 μL。离子源:ESI源;扫描方式:多反应监测(MRM)方式,扫描时间为0.1 s;毛细管电压:2.5 kV;锥孔电压:26 V;离子源温度:110 ℃;去溶剂气温度:350 ℃;去溶剂气流量:500 L/h;锥孔气流量:50 L/h。采用回归方程计算血浆中阿糖尿苷。SD大鼠尾iv注射用盐酸阿糖胞苷,制备血药质量浓度–时间曲线,计算药动学参数。结果 阿糖尿苷在1.0~1 000 ng/mL线性关系良好,日内、日间RSD值均小于15%,准确度在±15%,平均提取回收率在90%以上,基质效应在97.3%,稳定性良好。药动学参数:tmax是1.0 h,Cmax是134.2 ng/mL,AUC0-t是2 316.0 ng•h/mL,t1/2是4.3 h。结论 该方法适合大鼠尾iv阿糖胞苷后阿糖尿苷在体内的药动学研究。
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[Abstract]
Objective To develop an LC-MS/MS method for the determination of uridine in rat plasma, and study in vivo pharmacokinetics of uridine in rats administered with Cytarabine Hydrochloride for injection. Methods LC-MS/MS method was used. The HPLC analysis was separated on an Acquity UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm). The mobile phase was water - acetonitrile with gradient elution. The column temperature was 20 ℃ with injection volume of 10 μL at a flow rate of 0.2 mL/min. MS conditions were that a triple-quadrupole mass spectrometry equipped with electrospray ionization (ESI) source for detection and multiple reaction monitoring (MRM) were applied with sweep time of 0.1 s. Capillary voltage and cone voltage were 2.5 kV and 26 V. The temperature was 110 ℃. The temperature and flow rate of the solvent gas (N2) were 350 ℃ and 500 L/h. The flow rate of cone gas was 50 L/h. Contents of uridine in samples were determined with regression equation of standard curves. The blood concentration - time curve was investigated after tail iv administration of Cytarabine Hydrochloride for injection to SD rats, then the pharmacokinetic parameters were calculated.Results The linearity range of uridine was 1 - 1 000 ng/mL. The intra- and inter-day relative standard deviation (RSD) were less than 15% and the relative error (RE) were all within 15%. The average extraction recovery was over 90%. The result of matrix effects was 97.3%, and it had good stability. Parameters of pharmacokinetics were tmax 1.0 h, Cmax 134.2 ng/mL, AUC0-t 2 316.0 ng•h/mL, and t1/2 4.3 h. Conclusion The method is successfully applied to pharmacokinetic study of uridine translated from cytarabine in rats administered with Cytarabine Hydrochloride for injection.
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