摘要
目的建立高效液相色谱串联质谱法同时测定临床血浆中甲氨蝶呤和万古霉素的浓度,并用于儿童患者治疗药物监测。方法血浆样本经乙腈沉淀蛋白前处理,用C18色谱柱分离,流动相为0.1%甲酸水和乙腈,梯度洗脱,流速为0.55 mL·min^(-1)。质谱检测方式为正离子模式,多反应监测扫描,监测甲氨蝶呤m/z 455.1→m/z 308.2,甲氨蝶呤-d3 m/z 458.1→m/z 311.1(内标);万古霉素m/z 725.4→m/z 144.2,去甲万古霉素m/z 718.5→m/z 144.2(内标)。结果甲氨蝶呤浓度在25~1500 ng·mL^(-1)与峰面积线性关系良好(r=0.9988),万古霉素浓度在1~50μg·mL^(-1)与峰面积线性关系良好(r=0.9988)。准确度、精密度、基质效应和稳定性均符合要求。结论本方法操作简便快速准确专属性强且稳定性良好,适用于人血浆中甲氨蝶呤和万古霉素的分析,可用于儿童患者临床治疗药物监测。
Objective To establish a high performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of methotrexate and vancomycin in clinical plasma and to monitor therapeutic drugs in children.Methods The plasma samples were pretreated with acetonitrile precipitated protein and separated on a C18 column with mobile phases consisting of 0.1%formic acid and acetonitrile.The flow rate was 0.55 mL·min^(-1).The detection method of mass spectrometry was positive ion mode,multi-reaction monitoring scan,monitoring methotrexate m/z 455.1→m/z 308.2,methotrexate d3 m/z 458.1→m/z 311.1(internal standard);vancomycin m/z 725.4→m/z 144.2,norvancomycin m/z 718.5→m/z 144.2(internal standard).Results There was a good linear relationship between the peak area and the concentration of methotrexate in the range of 25-1500 ng·mL^(-1)(r=0.9988),and the concentration of vancomycin in the range of 1-50μg·mL^(-1)(r=0.9988).Accuracy,precision matrix effect and stability meet the requirements.Conclusion This method is simple,rapid,accurate,specific and stable.It is suitable for the analysis of methotrexate and vancomycin in human plasma,and can be used for the monitoring of clinical therapeutic drugs in children.
作者
秦亚彬
李瑞宏
刘少卿
郑清芬
张古英
赵德运
QIN Ya-bin;LI Rui-hong;LIU Shao-qing;ZHENG Qing-fen;ZHANG Gu-ying;ZHAO De-yun(Department of Pharmacy,Children's Hospital of Hebei Province,Shijiazhuang 050031,Hebei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第1期111-114,共4页
The Chinese Journal of Clinical Pharmacology
基金
河北省卫健委医学科学研究课题计划基金资助项目(20190795)。
