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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,1.7μm);流动相:水–乙腈,梯度洗脱;体积流量:0.2 mL/min;柱温:40℃;进样量:5μL。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。
OBJECTIVE To establish a LC-MS / MS method for the determination of arabinouridine in rat plasma for the pharmacokinetic study of arabinouridine in rat tail iv injection of cytarabine hydrochloride. Methods LC-MS / MS method. ACQUITY UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm); mobile phase: water-acetonitrile gradient elution; volume flow rate: 0.2 mL / min; column temperature: 40 ° C .; injection volume: 5 μL. Ion source: ESI source; Scanning method: Multiple reaction monitoring (MRM) method, scanning time: 0.1 s; Capillary voltage: 2.5 kV; Cone voltage: 26 V; Ion source temperature: 110 ° C .; Desolvation temperature: 350 ° C ; To solvent gas flow: 500 L / h; Cone flow: 50 L / h. The regression equation was used to calculate the plasma arabinoside. Sprague-Dawley rats were iv injected with cytarabine hydrochloride to prepare the plasma concentration-time curve and calculate the pharmacokinetic parameters. Results The linearity of uridine was 1.0-1 000 ng / mL. The intra-day and inter-day RSD values were less than 15% and the accuracy was ± 15%. The average extraction recovery was over 90% and the matrix effect was stable at 97.3% Good sex. Pharmacokinetic parameters: tmax was 1.0 h, Cmax was 134.2 ng / mL, AUC0-t was 2 316.0 ng · h / mL and t1 / 2 was 4.3 h. Conclusion This method is suitable for the pharmacokinetics of arabinouridine in rats after iv iv cytarabine.