摘要
目的:建立同时测定晚期结直肠癌患者血浆中伊立替康(CPT-11)及其活性代谢产物7-乙基-10-羟基喜树碱(SN-38)和非活性代谢产物的SN-38葡萄糖醛酸化(SN-38G)的浓度测定方法,并进行方法学验证。方法:以Kromacil C_(18)为色谱柱,甲醇-水(含5 mmol·L^(-1)KH_2PO_3,p H=3.0)=55∶45为流动相,激发波长λ_(ex)=385 nm、发射波长λ_(em)=535 nm。结果:CPT-11在20~5000 ng·m L^(-1)范围内线性良好,SN-38在2~500 ng·m L^(-1)范围内线性良好,r值均为0.999。CPT-11和SN-38的提取回收率分别为53.26%~59.86%和66.83%~71.30%。CPT-11低、中、高三种浓度的日间和日内精密度均小于6.32%;SN-38低、中、高三种浓度的日间和日内精密度均小于7.02%。血浆样品反复冻融3次、室温放置8 h、进样器中放置24 h及长期冻融,稳定性均良好,样品浓度均未见显著改变。结论:使用高效液相色谱-荧光定量检测法简便、准确、灵敏,适用于晚期结直肠癌患者血浆中伊立替康及其代谢产物SN-38、SN-38G的血药浓度测定。
Objective: To establish and validate a method for simultaneous determination of irinotecan(CPT-11) and its active metabolite SN-38 and inactive metabolite SN-38 G in plasma of metastatic colorectal cancer patients by HPLC-FLD. Methods: Chromatographic separation was performed on a Kromacil C_(18) column, using methanol(5 mmol·L^(-1)KH_2PO_3, p H=3.0): water=55∶45 as mobile phase. The detection wavelengths were: λ_(ex)=385 nm, λ_(e m)=535 nm. Results: The assay was linear at the range 20-5000 ng·m L^(-1)for CPT-11(r=0.999) and 2-500 ng·m L^(-1)for SN-38(r=0.999). The extraction recoveries were between 53.26%-59.86% for CPT-11, and between 66.83%-71.30% for SN-38, respectively. Both intra- and inter-day precisions for CPT-11 were within 6.32%. Both intra- and inter-day precisions for SN-38 were with 7.02%.The spiked samples were stable after three freeze-thaw cycles, at room temperature for 8h or in auto sample bottles for 24 h. The changes in levels of CPT-11 and SN-38 after long-term stability test were not obvious. Conclusion: The HPLC-FLD method for detection of CPT-11 and its metabolites SN-38 and SN-38 G in plasma of metastatic colorectal cancer patients is simple, accurate and sensitive.
出处
《药学与临床研究》
2015年第6期565-568,共4页
Pharmaceutical and Clinical Research
基金
江苏省药学会-奥赛康医院药学基金"伊立替康对晚期结直肠癌患者合理用药研究"(项目编号:201312)
