目的 建立測(cè)定大鼠血漿中阿糖尿苷的LC-MS/MS方法，用于大鼠尾iv注射用鹽酸阿糖胞苷后阿糖尿苷在體內(nèi)的藥動(dòng)學(xué)研究。方法 采用LC-MS/MS法。ACQUITY UPLC BEH C₁₈色譜柱（50 mm×2.1 mm，1.7 μm）；流動(dòng)相：水–乙腈，梯度洗脫；體積流量：0.2 mL/min；柱溫：40 ℃；進(jìn)樣量：5 μL。離子源：ESI源；掃描方式：多反應(yīng)監(jiān)測(cè)（MRM）方式，掃描時(shí)間為0.1 s；毛細(xì)管電壓：2.5 kV；錐孔電壓：26 V；離子源溫度：110 ℃；去溶劑氣溫度：350 ℃；去溶劑氣流量：500 L/h；錐孔氣流量：50 L/h。采用回歸方程計(jì)算血漿中阿糖尿苷。SD大鼠尾iv注射用鹽酸阿糖胞苷，制備血藥質(zhì)量濃度–時(shí)間曲線，計(jì)算藥動(dòng)學(xué)參數(shù)。結(jié)果 阿糖尿苷在1.0～1 000 ng/mL線性關(guān)系良好，日內(nèi)、日間RSD值均小于15%，準(zhǔn)確度在±15%，平均提取回收率在90%以上，基質(zhì)效應(yīng)在97.3%，穩(wěn)定性良好。藥動(dòng)學(xué)參數(shù)：t_max是1.0 h，C_max是134.2 ng/mL，AUC_0-t是2 316.0 ng•h/mL，t_1/2是4.3 h。結(jié)論 該方法適合大鼠尾iv阿糖胞苷后阿糖尿苷在體內(nèi)的藥動(dòng)學(xué)研究。

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 t_max 1.0 h, C_max 134.2 ng/mL, AUC_0-t 2 316.0 ng•h/mL, and t_1/2 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.