中国药物警戒 ›› 2010, Vol. 7 ›› Issue (4): 196-198.

• 基础研究 • 上一篇    下一篇

内标法测定甲氨蝶呤血药浓度及其在小剂量甲氨蝶呤应用的监测

李明艳, 吴洪文   

  1. 广西医科大学第四附属医院,广西 柳州 545005
  • 收稿日期:2016-02-19 修回日期:2016-02-19 出版日期:2010-04-08 发布日期:2016-02-19
  • 作者简介:李明艳,女,本科,主管药师,临床药学。

Determination of Serum Methotrexate Concentration with Internal Standard Method and Its Apply in Low-dose Methotrexate Therapy

LI Ming-yan, WU Hong-wen   

  1. The 4th Affiliated Hospital of Guangxi Medical University, Guangxi Liuzhou 545005, China
  • Received:2016-02-19 Revised:2016-02-19 Online:2010-04-08 Published:2016-02-19

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摘要： 目的 建立内标法测定甲氨蝶呤血药浓度并应用于小剂量甲氨蝶呤治疗的监测中,以考察血药浓度和不良反应发生的相关性。方法 通过高效液相色谱法,用甲硝唑作内标测定甲氨蝶呤血药浓度。色谱柱为SHIMADZU VP-ODS C18（250mm×4.6mm, 5 m）,流动相为甲醇-pH3.5醋酸钠缓冲液（10 90）,流速为1.0 mL/min,检测波长为306nm,室温为25℃。小剂量甲氨蝶呤治疗的患者在开始静脉滴注后1.5~2h内抽血测定血药浓度并随访跟踪患者不良反应的发生情况。结果 线性范围是20~1 000 g/L（r=0.9992,n=8）,日内日间精密度均小于15%。小剂量甲氨蝶呤治疗中,发生不良反应组的甲氨蝶呤血药浓度显著高于没有发生不良反应组。结论 本方法灵敏、快速, 准确, 在小剂量甲氨蝶呤治疗中应监测其血药浓度,实施个体化给药。

关键词: 甲氨蝶呤, 血药浓度, 不良反应

Abstract: Objective To establish a internal standard method to determine the serum concentration of Methotrexate(MTX) and apply in the low-dose MTX therapy. Methods The serum MTX concentration was determined by HPLC, with metron-idazole as internal standard. The separation was carried out using Shimadzu VP-ODS C18(250mm×4.6mm, 5μm) column with mobile phase of methanol-sodium acetate buffer(pH3.5) (10:90) at a flow rate of 1.0mL/min． The detection wavelength was 306nm and the column temperature was 25℃． And the serum concentration was examined within 1.5~2h after intravenous injection of the patients who received low-dose MTX. Then the patients were followed-up to observe the adverse reaction. Rusults The linear range was 20~1 000μg/L(r=0.9992, n=8)． The intra-day and inter-day precision were both less than 15%. The serum MTX concentration in patients with adverse reactions were significantly higher than those without them. Conclusion The method is sensitive, rapid and accurate. We demonstrated that serum MTX concentration is worthy of detection in low-dose MTX therapy.

Key words: methotrexate, serum concentration, adverse reaction

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