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人血浆中甲氨蝶呤的高效液相色谱法测定及其代谢物的质谱定性分析

王漪璇,  毋丹,  曹军宁,  钱隽

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文章导航 > 药学实践与服务  > 2015 >  33(2): 143-146,158
王漪璇, 毋丹, 曹军宁, 钱隽. 人血浆中甲氨蝶呤的高效液相色谱法测定及其代谢物的质谱定性分析[J]. 药学实践与服务, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
引用本文: 王漪璇, 毋丹, 曹军宁, 钱隽. 人血浆中甲氨蝶呤的高效液相色谱法测定及其代谢物的质谱定性分析[J]. 药学实践与服务, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
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WANG Yixuan, WU Dan, CAO Junning, QIAN Jun. Determination of methotrexate in human plasma by HPLC and qualitative analysis of its metabolite by mass spectrometry[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
Citation: WANG Yixuan, WU Dan, CAO Junning, QIAN Jun. Determination of methotrexate in human plasma by HPLC and qualitative analysis of its metabolite by mass spectrometry[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
shu

人血浆中甲氨蝶呤的高效液相色谱法测定及其代谢物的质谱定性分析

doi: 10.3969/j.issn.1006-0111.2015.02.013

  • 复旦大学附属肿瘤医院肿瘤内科, 复旦大学上海医学院肿瘤学系, 上海 200032

Determination of methotrexate in human plasma by HPLC and qualitative analysis of its metabolite by mass spectrometry

  • Department of Medical Oncology, Cancer Hospital Affilliated to Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

  • 摘要: 目的 建立固相萃取-高效液相色谱法测定人血浆中的甲氨蝶呤浓度,用于临床治疗的监测,并通过质谱对甲氨蝶呤的人体代谢物进行定性分析。 方法 血浆样本经C18固相萃取小柱净化洗脱后直接进样,以Diamonsil C18分析柱(150 mm×4.6 mm, 5 m)分离,流动相为甲醇和0.5%乙酸溶液(含0.3%三乙胺),采用梯度洗脱;流速为1.0 ml/min;紫外检测波长为306 nm。通过质谱全扫描(QLMS)和多反应监测-信息关联采集-增强子离子扫描(MRM-IDA-EPI)获得甲氨蝶呤代谢物的质谱信息。 结果 甲氨蝶呤在0.05~100 μmol/L范围内线性关系良好(r=0.999 9),提取回收率>95%,准确度在97%~105%之间,日内与日间精密度(RSD)均<5%。分析甲氨蝶呤代谢物的质谱信息,推断该代谢物为7-羟基甲氨蝶呤。 结论 本方法灵敏度高、重现性好、操作简便,适用于甲氨蝶呤的血药浓度监测。
    Abstract: Objective To develop an SPE-HPLC method for the determination of methotrexate (MTX) in human plasma to monitor the clinical drug use of MTX, and to identify the human metabolite of MTX by mass spectrometry. Methods MTX was extracted from human plasma using C18 SPE column and analyzed directly after elution. The separation of MTX was performed on Diamonsil C18 column (150 mm×4.6 mm, 5 m) with a gradient mobile phase of methanol and 0.5% acetic acid solution (containing 0.3% triethylamine) at a flow rate of 1.0 ml/min. The detection wavelength was 306 nm. QLMS and MRM-IDA-EPI scan modes were used to obtain the mass spectrum of MTX metabolite. Results The calibration curve of MTX in plasma was linear over the range of 0.05-100 μmol/L(r=0.999 9). The extraction recovery was above 95% and accuracy was between 97% and 105%. Both intra-and inter-day precision were less than 5%. 7-OH MTX was identified to be the metabolite through the analysis of the mass spectrum. Conclusion The method is sensitive, reproducible, easy to operate and suits for monitoring the concentration of MTX in clinical practice.
  • [1] Green MR,Chowdhary S,Lombardi KM,et al.Clinical utility and pharmacology of high-dose MTX in the treatment of primary CNS lymphoma[J].Expert Rev Neurother,2006,6(5):635-652.
    [2] Lennard L.Therapeutic drug monitoring of antimetabolic cytotoxic drugs[J].Br J Clin Pharmacol,1999,47:131-143.
    [3] 彭 波.高效液相色谱法测定甲氨蝶呤的血药浓度[J].中国医院药学杂志,2011, 31 (11):951-952.
    [4] 张春燕,顾 健.反相高效液相色谱法同时测定人血浆中亚叶酸、5-甲基四氢叶酸及甲氨蝶呤的浓度及临床应用[J].中国药学杂志,2010,45(7):543-547.
    [5] 许耘川,袁向亮,沈立松.HPLC法测定血清甲氨蝶呤浓度的方法建立及其与荧光偏振法的比较[J].检验医学,2010,25(9):701-704.
    [6] 谢军平,冯玲玲,匡 霞.HPLC 测定大剂量甲氨蝶呤患者血药浓度[J].中国实验方剂学杂志,2010,16(11):69-72.
    [7] 霍 晶,袁盛华,方 芸,等.反相高效液相色谱法测定人血浆中甲氨蝶呤的浓度[J].药学与临床研究,2007,15(5):390-392.
    [8] Turci R,Micoli G,Minoia C.Determination of methotrexate in environmental samples by solid phase extraction and high performance liquid chromatography: ultraviolet or tandem mass spectrometry detection?[J].Rapid Commun Mass Spectr,2000,14:685-691.
    [9] 周 卿,潘雪君.固相萃取-高效液相色谱法测定人乳中甲氨蝶呤的含量[J].药物分析杂志,2011,31(12):2305-2307.
    [10] 吴雪梅, 丘宏强, 方令平, 等.固相萃取-高效液相色谱法测定甲氨蝶呤的血药浓度[J].中国医院药学杂志,2008,28(18):1617-1619.
    [JP2]张华年,文玲莉,张少文, 等.固相萃取高效液相色谱法检测生物样本中甲氨喋呤[J].药物分析杂志,2000,20(6):401-404.
    [12] 曹一辰,孟祥乐,朱金辉,等.LC-MS/MS法测定人血清中甲氨蝶呤及其代谢产物7-羟基甲氨蝶呤的浓度[J].中国药师,2012,15(2):191-194.
    [13] Guo PI, Wang XM, Liu LS, et al.Determination of methotrexate and its major metabolite 7-hydroxymethotrexate in mouse plasma and brain tissue by liquid chromatography-tandem mass spectrometry[J].J Pharm Biomed Anal,2007,43:1789-1795.
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  • 收稿日期:  2014-04-03
  • 修回日期:  2014-06-26

人血浆中甲氨蝶呤的高效液相色谱法测定及其代谢物的质谱定性分析

doi: 10.3969/j.issn.1006-0111.2015.02.013
  • 复旦大学附属肿瘤医院肿瘤内科, 复旦大学上海医学院肿瘤学系, 上海 200032
  • 收稿日期: 2014-04-03
  • 修回日期: 2014-06-26

摘要: 目的 建立固相萃取-高效液相色谱法测定人血浆中的甲氨蝶呤浓度,用于临床治疗的监测,并通过质谱对甲氨蝶呤的人体代谢物进行定性分析。 方法 血浆样本经C18固相萃取小柱净化洗脱后直接进样,以Diamonsil C18分析柱(150 mm×4.6 mm, 5 m)分离,流动相为甲醇和0.5%乙酸溶液(含0.3%三乙胺),采用梯度洗脱;流速为1.0 ml/min;紫外检测波长为306 nm。通过质谱全扫描(QLMS)和多反应监测-信息关联采集-增强子离子扫描(MRM-IDA-EPI)获得甲氨蝶呤代谢物的质谱信息。 结果 甲氨蝶呤在0.05~100 μmol/L范围内线性关系良好(r=0.999 9),提取回收率>95%,准确度在97%~105%之间,日内与日间精密度(RSD)均<5%。分析甲氨蝶呤代谢物的质谱信息,推断该代谢物为7-羟基甲氨蝶呤。 结论 本方法灵敏度高、重现性好、操作简便,适用于甲氨蝶呤的血药浓度监测。

English Abstract

王漪璇, 毋丹, 曹军宁, 钱隽. 人血浆中甲氨蝶呤的高效液相色谱法测定及其代谢物的质谱定性分析[J]. 药学实践与服务, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
引用本文: 王漪璇, 毋丹, 曹军宁, 钱隽. 人血浆中甲氨蝶呤的高效液相色谱法测定及其代谢物的质谱定性分析[J]. 药学实践与服务, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
shu
WANG Yixuan, WU Dan, CAO Junning, QIAN Jun. Determination of methotrexate in human plasma by HPLC and qualitative analysis of its metabolite by mass spectrometry[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
Citation: WANG Yixuan, WU Dan, CAO Junning, QIAN Jun. Determination of methotrexate in human plasma by HPLC and qualitative analysis of its metabolite by mass spectrometry[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 143-146,158. doi: 10.3969/j.issn.1006-0111.2015.02.013
shu

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