RP-HPLC法同时测定白血病患者血浆中奈拉滨及其代谢物  

Determination of Nelarabine and Its Metabolite in Leukemia Patients Plasma by RP-HPLC

作　　者：沈卫阳[1] 刘云鹏[1] 胡陈夷 张英琪[2] 

机构地区：[1]中国药科大学理学院药物质量与安全预警教育部重点实验室,南京211198 [2]江苏正大天晴药业股份有限公司,南京210023

出　　处：《药学与临床研究》2016年第2期117-120,共4页Pharmaceutical and Clinical Research

摘　　要：目的:建立HPLC法同时测定人体血浆中奈拉滨及其代谢物ara-G(9-β-D-阿糖呋喃糖鸟嘌呤),用于临床患者静脉滴注奈拉滨后血药浓度的监测和药动学研究。方法:内标药吉西他滨;色谱柱为Waters XBridge Shield RP18(4.6 mm×250 mm,5μm),流动相为5 mmol·L^(-1)乙酸铵水溶液-乙腈(乙酸调p H至4.0),梯度洗脱,柱温为40℃,检测波长为254 nm,流速为1.0 m L·min^(-1)。结果:奈拉滨与ara-G血药浓度分别在1~400μg·m L^(-1)、1~50μg·m L^(-1)范围内线性关系良好(r=0.999);低、中、高3个浓度的提取回收率在80%~95%;批内、批间精密度的RSD均小于5%。结论:本法简便、灵敏、回收率高、重复性好,可用于人体血浆中奈拉滨和ara-G的测定与药代动力学研究。Objective: To establish a RP-HPLC method for the determination of nelarabine and its active metabolite 9-β-D-arabinofuranosyl-guanine(ara-G) in human plasma in order to monitor their concentrations for pharmacokinetic studies. Methods: Gemcitabine was used as the internal standard. The contents of nelarabine and ara-G were detected by an ultraviolet detector at 254 nm with a Waters XBridge Shield RP18(4.6 mm×250 mm, 5 μm) column at a flow rate of 1.0 m L·min^(-1). The mobile phase was consisted of acetonitrile- 5 mmol·L^(-1)ammonium acetate buffer solution(p H adjusted to 4.0 by acetic acid) for gradient elution. The column temperature was 40 ℃. Results: The linear ranges of nelarabine and ara-G were 1-400 μg·m L^(-1)and 1-50 μg·m L^(-1)(r=0.999), respectively. Recoveries from plasma samples spiked with nelarabine and ara-G at three levels were 80%-95%. Both the inter-day and intra-day RSD were within5%. Conclusion: This method is simple, sensitive and reproducible. It can be used for the determination of nelarabine and ara-G in human plasma and their pharmacokinetic study.

关 键 词：奈拉滨 ara-G HPLC法 血药浓度 药代动力学 

分 类 号：R969.1[医药卫生—药理学]