文章摘要
周青,张晏洁,薛源,芮建中,周国华.LC-MS/MS法测定骨肉瘤患者血清中甲氨蝶呤及其 代谢产物7-羟基甲氨蝶呤的浓度[J].药学与临床研究,2021,29(4):267~270
LC-MS/MS法测定骨肉瘤患者血清中甲氨蝶呤及其 代谢产物7-羟基甲氨蝶呤的浓度
Determination of Methotrexate and Its Metabolite 7-Hydroxy-methotrexate in Osteosarcoma Patients Serum by LC-MS/MS
投稿时间:2021-03-01  修订日期:2021-08-13
DOI:
中文关键词: 甲氨蝶呤  7-羟基甲氨喋呤  高效液相色谱串联质谱法  治疗药物监测
英文关键词: Methotrexate  7-Hydroxy-methotrexate  LC-MS/MS  TDM
基金项目:国家自然科学基金(81901890)
作者单位E-mail
周青 东部战区总医院 qingchou0504@163.com 
张晏洁 东部战区总医院  
薛源 东部战区总医院  
芮建中 东部战区总医院  
周国华 东部战区总医院 ghzhou@nju.edu.cn 
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中文摘要:
      目的:建立测定人血清中甲氨喋呤及其代谢产物7-羟基甲氨喋呤浓度的LC-MS/MS法,并应用于骨肉瘤患者大剂量甲氨蝶呤化疗后的治疗药物监测,为临床合理用药提供依据。方法:以氨基蝶呤作为内标,血清样品经含内标甲醇沉淀蛋白处理。色谱柱为Agilent Zorbax Eclipse Plus C18;柱温35 °C;流速0.4 mL·min-1;流动相为含0.1%甲酸的水溶液和含0.1%甲酸的乙腈溶液,梯度洗脱。质谱检测方式为电喷雾离子阱正离子模式,MRM扫描,监测甲氨蝶呤m/z 455.098→308.000,7-羟基甲氨喋呤m/z 471.187→324.100,氨基蝶呤m/z 441.198→294.100。结果:甲氨蝶呤浓度在2~1000 ng·mL-1(r=0.998 5),7-羟基甲氨蝶呤浓度在20~10000 ng·mL-1(r=0.998 4)与峰面积线性关系良好。甲氨蝶呤、7-羟基甲氨蝶呤日内及日间RSD≤6.21%。甲氨蝶呤、7-羟基甲氨蝶呤的平均回收率分别为102.83%~119.34%、88.41%~95.37%。结论:本方法简便、准确、快速,适用于甲氨喋呤及其代谢产物7-羟基甲氨喋呤的血药浓度测定。
英文摘要:
      Objective: An LC-MS/MS method was established to determine methotrexate (MTX) and its metabolite 7-hydroxy-methotrexate (7-OH MTX) in osteosarcoma patients serum. Method: Methanol containing internal standard aminopterin was used as serum precipitant. An Agilent Zorbax Eclipse Plus C18 column was applied for HPLC at 35 ℃ with 0.1% formicacid and acetonitrile as the mobile phase gradiently eluted at a flow rate of 0.4 mL·min-1. Mass spectrometric analysis was performed in positive ion mode by multiple reaction monitoring (MRM) of the transitions at m/z 455.098→308.000 for MTX, m/z 471.187→324.100 for 7-OH MTX and m/z 441.198→294.100 for aminopterin, respectively. Results: The method was validated over concentration ranges of 2-1000 ng·mL-1 for MTX (r=0.9985) and 20-10000 ng·mL-1 for 7-OH MTX (r=0.9984), respectively. The intra-and inter-day precision and accuracy of the quality control samples exhibited relative standard deviations ≤6.21%. The mean extract recoveries were 102.83% to 119.34% for MTX and 88.41% to 95.37% for 7-OH MTX, respectively. Conclusion: The established method is convenient, accurate, rapid and reliable for the determination of MTX and 7-OH MTX in human serum.
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