首页|自主研制四极杆-线形离子阱质谱仪测定血清中甲氨蝶呤

自主研制四极杆-线形离子阱质谱仪测定血清中甲氨蝶呤

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
本研究基于自主研制的QLIT-6610MD液相色谱-四极杆-线形离子阱-质谱联用仪,建立了准确测量血清中甲氨蝶呤的同位素稀释质谱法.采用甲醇沉淀血清样品的蛋白后测定上清液.通过基质匹配标准曲线定量,在10～5 000 μg/L浓度范围内,甲氨蝶呤的线性系数R2＞0.999 0,定量限为 10 μg/L,质控品精密度优于 6.94%,血清样本添加回收率为 86.39%～97.84%,变异系数(CV)≤8.04%.应用QLIT-6610MD与AB QTRAP 6500+液相色谱-质谱联用仪同时测定 70例临床血清样本,并采用Pearson系数与BLand-ALtman法进行比较.结果表明,2台仪器所测结果一致,QLIT-6610MD可达到三重四极杆质谱仪定量测定血清中甲氨蝶呤的水平,能够满足临床诊断需求,为临床质谱分析提供了一种新的国产仪器选择.此外,本研究还初步探讨了多级碎裂技术(MSn)测定血清中甲氨蝶呤的可能性,为后续研究奠定基础.
Determination of Methotrexate in Serum by House-Made Quadrupole-Linear Ion Trap Mass Spectrometer
Methotrexate(MTX)is a therapeutic drug that is widely used in clinic for treatment of a variety of cancers.However,MTX has limited selectivity and serious cytotoxicity,at the same time,there are problems such as narrow therapeutic window and large individual variability in metabolism and excretion of MTX.Therefore,blood concentration monitoring is required for MTX administration in clinical practice.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)has the advantages of strong specificity,good separation characteristics,high sensitivity and fast detection speed,which has become the internationally recognized"gold standard"for blood concentration monitoring of drugs.In this study,an isotope dilution mass spectrometry method was developed for accurate measurement of MTX in serum by the house-made QLIT-6610MD quadrupole-linear ion trap liquid chromatography-mass spectrometer.Unlike the traditional triple quadrupole QqQ tandem mass spectrometer,the quadrupole-linear ion trap(Q-LIT)mass spectrometer adopts the quadrupole-linear ion trap direct axial coupling design,i.e.,a single linear ion trap is used to replace the QqQ tandem mass spectrometer's back-end fragmentation cell and the quadrupole,and no other components are installed between the quadrupole and linear ion trap,which greatly streamlines the quality and efficiency of the mass spectrometer while ensuring the original performance of the instrument.With this unique configuration,the QLIT-6610MD instrument uses a simultaneous fragmentation and accumulation technique,which remarkedly reduces matrix-induced interferences and effectively reduces space charge effects.Serum samples were pretreated with methanol to precipitate proteins and the supernatants were measured by QLIT-6610MD spectrometer.The linear correlation coefficient(R2＞0.999 0)is obtained for MTX in the range of 10-5 000 μg/L.The limit of quantification is 10 μg/L.The precision of the quality control is better than 6.94%,and the recoveries of spiked serum samples are 86.39%-97.84%with a coefficient of variation less than 8.04%.We used the QLIT-6610MD and AB QTRAP 6500+ liquid chromatography-mass spectrometers to analyze 70 clinical serum samples for comparison of the performance of the house-made instrument by means of Pearson's coefficient and BLand-ALtman method.The results showed that the QLIT-6610MD mass spectrometry achieves a similar level of performance to AB ATRAP 6500+ instrument,and provides a new domestic instrument option for clinical mass spectrometry.In addition,this study explores the possibility applying the multi-stage fragmentation technique(MSn)to determine MTX in serum,gaining fundamental data for future studies.

liquid chromatography-tandem mass spectrometry(LC-MS/MS)isotope dilution mass spectrometryquadrupolelinear ion trapmethotrexate(MTX)

刘粮泽、谢洁、屈子裕、易可可、张谛、黄泽建、鄢丹、戴新华、方向、时正媛、江游、俞晓平

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中国计量大学生命科学学院,浙江杭州 310018

中国计量科学研究院前沿计量科学中心,国家市场监管技术创新中心(质谱),北京 100029

首都医科大学附属北京世纪坛医院,北京 100038

液相色谱-串联质谱(LC-MS/MS) 同位素稀释质谱 四极杆 线形离子阱 甲氨蝶呤(MTX)

国家重点研发计划——重大科学仪器设备开发专项国家自然科学基金——国家重大科研仪器研制项目

2020YFF0101460021927812

2024

10.7538/zpxb.2023.0082

质谱学报
北京中科科仪技术发展有限责任公司 中国物理学会质谱分会

质谱学报

CSTPCD北大核心EI
影响因子：1.046
ISSN：1004-2997
年,卷(期)：2024.45(3)
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