LC-MS/MS法检测血液恶性肿瘤患者血清中甲氨蝶呤及其代谢物7-羟基甲氨蝶呤的浓度  

Simultaneous Determination of Methotrexate and 7-Hydroxy Methotrexate in Serum of Patients with Hematological Malignancies by LC-MS/MS

作　　者：胡楠[1] 钱卿[1] 恽琴素 周颀[2] 邹素兰[1] 蒋艳[1] Hu Nan;Qian Qing;Yun Qinsu;Zhou Qi;Zou Sulan;Jiang Yan(Department of Pharmacy,the First People’s Hospital of Changzhou,Jiangsu Changzhou 213003,China;Department of Oncology,the First People’s Hospital of Changzhou,Jiangsu Changzhou 213003,China)

机构地区：[1]常州市第一人民医院药剂科,江苏常州213003 [2]常州市第一人民医院肿瘤科,江苏常州213003

出　　处：《中国药师》2020年第5期910-913,共4页China Pharmacist

基　　金：国家自然科学基金项目(编号:81503136);江苏省药学会-奥赛康医院药学基金项目(编号:A201514);常州市四药临床药学科研基金指导性项目(编号:2015272、2017332);常州市第二十五批科技计划(科技服务体系)项目(编号:CF20170010)。

摘　　要：目的:采用高效液相色谱串联质谱法(LC-MS/MS)法检测血液恶性肿瘤患者血清中甲氨蝶呤(MTX)及其代谢物7-羟基甲氨蝶呤(7-OH MTX)的浓度。方法:选取2017年1月~2018年12月进行大剂量MTX(HDMTX,1.5~2.0 g·m-2)化疗的血液恶性肿瘤患者共12例,于HDMTX滴注结束后第0,24,48,72,96 h分别取静脉血2 ml,LC-MS/MS法同时检测血清中MTX及7-OH MTX的浓度。结果:HDMTX滴注结束后0,24,48,72,96 h MTX浓度分别为(21.292±17.574),(0.438±0.860),(0.067±0.075),(0.020±0.002),(0.008±0.002)μmol·L-1,7-OH MTX浓度分别为(5.586±2.668),(1.136±1.593),(0.279±0.367),(0.097±0.128),(0.040±0.051)μmol·L-1,其中0 h时MTX浓度大于7-OH MTX,而24~96 h各时间点MTX浓度均小于7-OH MTX,7-OH MTX/MTX浓度比值分别是2.6,4.2,4.9和5.0。结论:HDMTX滴注结束24 h后,体内代谢物7-OH MTX浓度高于MTX数倍,提示检测7-OH MTX浓度具有一定的临床意义。Objective:To determine the concentration of methotrexate(MTX)and its metabolite 7-hydroxymethoxazole(7-OH MTX)in serum of patients with hematological malignancies by LC-MS/MS.Methods:A total of 12 patients with hematologic malignancies who received HDMTX(1.5-2.0 g·m-2)chemotherapy from January 2017 to December 2018 were enrolled in our hospital.Blood(2 ml)was withdrawn from the patients at 0,24,48,72 and 96 h after the end of 24 h HDMTX instillation.The concentrations of MTX and 7-OH MTX in serum were detected by LC-MS/MS.Results:The concentration of MTX was 21.292±17.574,0.438±0.860,0.067±0.075,0.020±0.002 and 0.008±0.002μmol·L-1 respectively at 0,24,48,72 and 96 h after the end of HDMTX instillation,while the concentration of 7-OH MTX was 5.586±2.668,1.136±1.593,0.279±0.367,0.097±0.128 and 0.040±0.05μmol·L-1,respectively.The MTX concentration was higher than that of 7-OH MTX at 0 h,however,the MTX concentration was lower than that of 7-OH MTX during 24 and 96 h,and the concentration of 7-OH MTX was 2.6,4.2,4.9 and 5.0 times of that of MTX,respectively.Conclusion:At 24h after the end of HBDTX infusion,the concentration of 7-OH MTX is higher than that of MTX,suggesting that the detection of 7-OH MTX concentration has certain clinical significance.

关 键 词：血液恶性肿瘤 高效液相色谱串联质谱法 甲氨蝶呤 大剂量 7-羟基甲氨蝶呤 

分 类 号：R969.1[医药卫生—药理学]