柱前衍生化法UPLC-MS/MS检测肿瘤患者不同化疗周期顺铂血药浓度  

Pre-column derivatization UPLC-MS/MS for detecting the plasma concentration of cisplatin in cancer patients with different chemotherapeutic cycles

作　　者：张靖悦 张琳琳[2] 王园芝 李晓纯 袁恒杰[1] ZHANG Jing-yue;ZHANG Lin-lin;WANG Yuan-zhi;LI Xiao-chun;YUAN Heng-jie(Department of Pharmacy,General Hospital,Tianjin Medical University,Tianjin 300052,China;Department of Medical Oncology,General Hospital,Tianjin Medical University,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院,药剂科,天津300052 [2]天津医科大学总医院,肿瘤科,天津300052

出　　处：《中国医院药学杂志》2021年第19期1962-1966,共5页Chinese Journal of Hospital Pharmacy

摘　　要：目的:建立定量检测肿瘤患者血浆中顺铂浓度的柱前衍生化超高效液相色谱-串联质谱(UPLC-MS/MS)法,比较顺铂(75 mg·m^(-2)·d^(-1))QD*1 d和(25 mg·m^(-2)·d^(-1))QD*3 d在不同化疗周期顺铂血药浓度的变化。方法:血浆样品的顺铂与二乙基二硫代氨基甲酸钠(DDTC)络合生成Pt(DDTC)衍生化产物,经蛋白沉淀后,采用UPLC-MS/MS测定,色谱柱为BEH C18(2.1 mm×50.0 mm, 1.7μm),流动相为乙腈-0.1%甲酸水,梯度洗脱,流速为0.35 mL·min-1,采用电喷雾正离子模式,以多反应监测(MRM)定量分析。结果:顺铂在20~3 000 ng·mL^(-1)(r^(2)=0.995 4)具有良好的线性范围;批内RSD在7.21%~12.06%,批间RSD在4.64%~11.17%;提取回收率为78.48%~99.2%,基质效应在90.7%~94.8%,稳定性良好。顺铂(75 mg·m^(-2)·d^(-1))QD*1 d在整个化疗周期中血药浓度呈上升趋势,顺铂(25 mg·m^(-2)·d^(-1))QD*3 d血药浓度呈下降趋势。结论:本研究建立的方法专属性高、稳定性好,适用于肿瘤患者血浆中顺铂浓度的检测。OBJECTIVE To establish pre-column derivatization ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) for quantitatively detecting the plasma concentration of cisplatin in cancer patients and comparing the changes of cisplatin blood concentration between cisplatin(75 mg·m^(-2)·d^(-1)) QD*1 d and(25 mg·m^(-2)·d^(-1)) QD*3 d in different chemotherapeutic cycles.METHODS Cisplatin in plasma sample was conjugated with sodium diethyldithiocarbamate(DDTC) to form a Pt(DDTC) derivatization product. It was determined by UPLC-MS/MS after protein precipitation. The column was composed of BEH C18(2.1 mm×50.0 mm, 1.7 μm), mobile phase acetonitrile-0.1% formic acid water, gradient elution, flow rate 0.35 mL·min-1 and electrospray positive ion mode. Quantitative analysis was performed by multiple reaction monitoring(MRM).RESULTS Cisplatin had a decent linear range of 20-3 000 ng·mL^(-1)(r^(2)=0.995 4);intra-assay RSD 7.21% to 12.06%, inter-assay RSD 4.64% to 11.17%;extraction recovery rate 78.48%-99.2%, matrix effect 90.7%-94.8% and stability excellent. The blood concentration of cisplatin(75 mg·m^(-2)·d^(-1)) QD*1 d showed an upward trend during an entire chemotherapeutic cycle and blood concentration of cisplatin(25 mg·m^(-2)·d^(-1)) QD*3 d had a downward trend.CONCLUSION With high specificity and decent stability, the above method may be employed for detecting the plasma level of cisplatin in cancer patients.

关 键 词：柱前衍生化法 超高效液相色谱-串联质谱 顺铂 

分 类 号：R917[医药卫生—药物分析学]