摘要
目的建立人血浆中甲氨蝶呤（MTX）浓度测定的液质联用方法,并应用于临床MTX浓度监测。方法血清用甲醇沉淀蛋白,内标选择噻氯匹定（IS）,色谱柱为Kromasil C8（50 mm×2.1 mm,5μm）,流速0.6 m L·min-1,流动相为含0.1%甲酸的甲醇和水,梯度洗脱,柱温40℃。质谱在ESI正离子模式下使用MRM扫描方式,MTX和IS的离子对分别为：m/z 455.2〉308.2和m/z 264.1〉154.0。结果 MTX浓度在0.01~1μmol·L-1内线性良好,日内和日间的精密度和准确度均在±15%内。MTX在低、中和高浓度的回收率为92.2%~100.5%,10倍和100倍稀释不影响测定结果并且在所有测定的条件下均稳定。结论本研究建立的液质联用测定MTX血浆浓度的方法快速、简便、准确、稳定,适用于MTX的临床药物浓度监测和药动学研究。
Objective To establish an HPLC-MS/MS method for the determination of methotrexate （MTX） in human plasma for clinical therapeutic drug monitoring of MTX. Methods The plasma was precipitated by methanol with ti- clopidine as the internal standard. A Kromasil C8 （50 mm × 2.1 mm, 5μm） column was used with water and methanol （both contain 0.1% formic acid） as the mobile phase at a flow rate of 0.6 mL· min^- 1, gradient elution at 40 ℃. MRM transi- tions were performed at m/z 455.2 〉 308.2 for MTX and m/z 264.1〉 154.0 for the IS under ESI positive ionization. Results The linearity of calibration curve was very good at 0.01 - 1μmol · L^-1. The recovery of MTX at 3 quality control levels was at 92.2% -- 100.5%. The dilution did not affect the accuracy and precision of the sample when the dilution factor was 10 and 100, and MTX was stable under all testing conditions. Conclusion The HPLC-MS/MS method for the determination of MTX in human plasma is rapid, stable, convenient, and accurate, which is suitable for clinical therapeutic drug monitoring and pharmacokinetic study of MTX.
出处
《中南药学》
CAS
2015年第10期1025-1029,共5页
Central South Pharmacy
基金
国家自然科学基金(No.81301118)
多肽及小分子药物北京市重点实验室开放课题(No.2014DTYW03)
作者简介
作者简介：朱乐亭，女，主管药师，主要从事药物分析和治疗药物监测研究，Tel：（010）67096862，E-mail：zhuzhu6862@126．com
通讯作者：梅升辉，男，博士，药师，主要从事药物化学和药物分析研究，Tel：（010）67096857，E-mail：meishenghui1983@126．com
