HPLC-荧光法测定人血浆中伊立替康及其活性代谢产物的浓度

发布时间：2018-09-19 19:38

【摘要】：目的:建立同时测定人血浆中伊立替康(CPT-11)及其活性代谢产物7-乙基-10-羟基喜树碱(SN-38)浓度的方法。方法:血浆样品经乙腈沉淀蛋白及盐酸酸化后,以喜树碱为内标,采用高效液相色谱-荧光法测定。色谱柱为Waters Luna C_(18),流动相为0.05 mol/L磷酸二氢钠溶液-乙腈(70∶30,V/V,用磷酸调节pH至4.0),流速为1 mL/min,激发波长为380 nm,发射波长为480 nm(CPT-11)、535 nm(SN-38),柱温为25℃,进样量为20μL。结果:CPT-11和SN-38血药浓度分别在200~1 000、5~45 ng/mL范围内线性关系良好(r分别为0.999 4、0.999 2,n=5),定量下限分别为200、5 ng/mL;日内、日间RSD为1.68%~5.57%;CPT-11和SN-38的相对回收率分别为90.12%~106.93%(RSD8%,n=5)、92.07%~102.56%(RSD6%,n=5),提取回收率分别为72.23%~86.56%(RSD6%,n=5)、71.98%~83.44%(RSD7%,n=5)。采用该方法测得5例结肠癌患者体内CPT-11和SN-38的血药浓度分别为431.13~617.19、13.97~31.89 ng/mL(静脉滴注结束后1 h),398.14~584.43、11.61~29.94 ng/mL(静脉滴注结束后2 h)。结论:该方法样品处理简单、快速,且灵敏度高、重复性好,适用于临床常规监测CPT-11及其代谢物SN-38的血药浓度及药动学研究。
[Abstract]:OBJECTIVE: To establish a method for the simultaneous determination of irinotecan (CPT-11) and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) in human plasma. METHODS: Plasma samples were acidified by acetonitrile and precipitated by hydrochloric acid. Camptothecin was used as internal standard for the determination by high performance liquid chromatography-fluorescence spectrometry. 5 mol/L sodium dihydrogen phosphate solution-acetonitrile (70:30, V/V, pH adjusted by phosphoric acid to 4.0), flow rate was 1 mL/min, excitation wavelength was 380 nm, emission wavelength was 480 nm (CPT-11), 535 nm (SN-38), column temperature was 25, injection volume was 20 mu L. Results: The plasma concentrations of CPT-11 and SN-38 had good linear relationship in the range of 200-1 000, 5-45 ng/mL (r were 0.999, 0-45 ng/mL, respectively). The relative recoveries of CPT-11 and SN-38 were 90.12% ~ 106.93% (RSD 8%, n = 5), 92.07% ~ 102.56% (RSD 6%, n = 5), 72.23% ~ 86.56% (RSD 6%, n = 5), 71.98% ~ 83.44% (RSD 7%, n = 5), respectively. The plasma concentrations of N-38 were 431.13~617.19, 13.97~31.89 ng/mL (1 hour after the end of intravenous drip), 398.14~584.43, 11.61~29.94 ng/mL (2 hours after the end of intravenous drip). Conclusion: The method is simple, rapid, sensitive and reproducible, and suitable for routine clinical monitoring of CPT-11 and its metabolite SN-38. Study.
【作者单位】：河北北方学院药学系;河北北方学院附属第一医院药剂科;
【基金】：河北省医学科学研究重点课题计划(No.20120157)
【分类号】：R969

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