HPLC-MS/MS法同时测定儿童血浆中万古霉素和地高辛的浓度  

HPLC-MS/MS method for the simultaneous determination of vancomycin and digoxin in children’s plasma

作　　者：秦亚彬 姜锡娟 张古英[1] 于斌[2] 邢冬[2] 秦皓[2] 白宗江 韩雨 QIN Ya-bin;JIANG Xi-juan;ZHANG Gu-ying;YU Bin;XING Dong;QIN Hao;BAI Zong-jiang;HAN Yu(Department of Pharmacy,Hebei Children’s Hospital,Shijiazhuang 050031;The Fourth Affiliated Hospital of Hebei Medical University,Shijiazhuang 050011)

机构地区：[1]河北省儿童医院药学部,石家庄050031 [2]河北医科大学第四医院,石家庄050011

出　　处：《中南药学》2024年第5期1385-1389,共5页Central South Pharmacy

基　　金：河北省医学科学研究课题计划(No.20221335,No.20200658)。

摘　　要：目的建立同时测定血浆中万古霉素和地高辛浓度的高效液相色谱串联质谱(HPLC-MS/MS)法,并用于儿童患者治疗药物监测。方法血浆样本经甲醇沉淀蛋白前处理,分别以去甲万古霉素和地高辛-d3作为内标,采用EVO-C18色谱柱分离,流动相为水(含0.02%甲酸和2 mmol·L^(-1)乙酸铵)和甲醇,梯度洗脱,流速为0.55 mL·min^(-1)。质谱检测方式为ESI正离子模式,dMRM扫描。结果万古霉素在1~50μg·mL^(-1)与峰面积线性关系良好(R^(2)>0.991),地高辛在0.25~8 ng·mL^(-1)与峰面积线性关系良好(R^(2)>0.993)。方法准确度、精密度、基质效应和稳定性均符合要求,并成功应用于311个样本的测定。结论本方法操作简便、快速、灵敏度高,适用于人血浆中万古霉素和地高辛浓度的同时分析,可用于儿童患者临床治疗药物监测。Objective To establish an HPLC-MS/MS method for the simultaneous determination of vancomycin and digoxin in children’s plasma,and to monitor children therapeutic drugs.Methods The plasma sample protein were precipitated by methanol with the norvancomycin and digoxin-d3 as the internal standards.The analytes were gradient eluted on an EVO-C18 column by HPLC-MS/MS,with the mobile phase consisting of water(0.02%formic acid and 2 mmol·L^(-1) ammonium acetate)-methanol at the flow rate of 0.55 mL·min^(-1).Ions were monitored in the dynamic multiple reaction monitoring(dMRM)mode,with positive ion electrospray ionization(ESI).Results Calibration plots were established over the concentration range of 1~50μg·mL^(-1 )for vancomycin(R^(2)>0.991),while 0.25~8 ng·mL^(-1) for digoxin(R^(2)>0.993).The accuracy,precision,matrix effect and stability all met the requirements.This method was fully verified and used to determine the drug concentrations in 311 plasma samples.Conclusion The method is simple,rapid,sensitive and suitable to monitorthe vancomycin and digoxin in children’s plasma.

关 键 词：万古霉素 地高辛 高效液相色谱串联质谱法 治疗药物监测 儿童 

分 类 号：R917[医药卫生—药物分析学] R96[医药卫生—药学]