LC-MS/MS法测定人血浆中地高辛的浓度及其在儿童患者中的应用

夏颖; 龙佳奕; 代浩然; 沈梦元; 郭宏丽; 胡雅慧; 陈峰

doi:10.11665/j.issn.1000-5048.20210610

LC-MS/MS法测定人血浆中地高辛的浓度及其在儿童患者中的应用

1.
南京医科大学附属儿童医院药学部药学研究中心，南京 210008
2.
中国药科大学础医学与临床药学学院，南京 210009
3.
南京医科大学康达学院，连云港 222000

基金项目: 江苏卫生健康委员会特聘医学专家项目资助（2019）#南京医科大学康达学院本科实习生

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出版历程
- 收稿日期: 2021-08-23
- 修回日期: 2021-11-03
- 刊出日期: 2021-12-24

Determination of digoxin in human plasma by LC-MS/MS and its application in pediatric patients

1.
Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing 210008
2.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009
3.
Kangda College of Nanjing Medical University, Lianyungang 222000 , China

Funds: This study was supported by Specially-Appointed Medical Expert Project of Jiangsu Provincial Commission of Health (2019)

摘要

摘要: 建立了简单、快速、可靠的LC-MS/MS法测定人血浆中地高辛的浓度。以地高辛-d3为内标，血浆样品经液液萃取法处理后进样。色谱柱为Kinetex C₁₈（2.1 mm × 50 mm， 2.6 μm； Phenomenex），流动相为均含1 mmol/L醋酸铵和1 mmol/L甲酸的水溶液和乙腈溶液（55∶45），采用等度洗脱，样品运行时间仅为2 min。选择TripleQuad? 4500MD质谱仪，在电喷雾离子化方式下（ESI），以正离子模式进行多重反应监测（MRM），地高辛及其内标的监测离子对分别为m/z 798.5 → 651.3和m/z 801.6 → 654.4。结果表明，在0.100~20.0 ng/mL范围内，标准曲线线性关系良好，该方法选择性好，准确度、精密度符合要求，各浓度水平提取回收率平行，稳定性良好，无基质效应等影响。该方法成功用于接受地高辛治疗的患儿的血样检测，可更大程度增加疗效、避免毒性反应，为临床个体化用药提供指导和依据。
- 地高辛 /
- LC-MS/MS /
- 儿童 /
- 含量测定
Abstract: The aim of the study was to develop a simple, rapid and accurate LC-MS/MS method for the determination of digoxin.Digoxin-d3 was taken as the internal standard (IS), and sample preparation was achieved by liquid-liquid extraction.Chromatographic separation was performed on a Kinetex C₁₈ column (2.1 mm × 50 mm, 2.6 μm; Phenomenex) using an isocratic elution with merely 2 min for each sample.The mobile phase consisted of water and acetonitrile solutions, both containing 1 mmol/L ammonium acetate and 1 mmol/L formic acid (55∶45).The detection was conducted on a TripleQuad^TM 4500MD mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring mode.The transitions were m/z 798.5 → 651.3 and m/z 801.6 → 654.4 for digoxin and digoxin-d3, respectively.Results showed that the method was linear over the range of 0.100-20.0 ng/mL.The selectivity, accuracy and precision, recovery and stability of the method were all within the acceptable limits with no matrix effect.This method was successfully applied to a girl treated with digoxin with substantial improvement of therapeutic effect and elimination of toxic reaction, so it can provide valuable fuidance and reference for individualized medication in clinical practice.
- digoxin /
- LC-MS/MS /
- children /
- determination of contents

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