Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring
Abstract Therapeutic drug monitoring (TDM) is necessary for the optimal administration of anti-arrhythmic drugs in the treatment of heart arrhythmia. The present study aimed to develop and validate a direct analysis in real time tandem mass spectrometry (DART–MS/MS) method for the rapid and simultan...
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2020-09-01
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Online Access: | https://doi.org/10.1038/s41598-020-72490-w |
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doaj-385224b5c9f14bb1bbfb7fe826e73ea52021-09-26T11:25:26ZengNature Publishing GroupScientific Reports2045-23222020-09-0110111010.1038/s41598-020-72490-wDirect analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoringYuzhou Gui0Youli Lu1Shuijun Li2Mengqi Zhang3Xiaokun Duan4Charles C. Liu5Jingying Jia6Gangyi Liu7Central Laboratory, Shanghai Xuhui Central HospitalCentral Laboratory, Shanghai Xuhui Central HospitalCentral Laboratory, Shanghai Xuhui Central HospitalCentral Laboratory, Shanghai Xuhui Central HospitalASPEC Technologies LimitedASPEC Technologies LimitedCentral Laboratory, Shanghai Xuhui Central HospitalCentral Laboratory, Shanghai Xuhui Central HospitalAbstract Therapeutic drug monitoring (TDM) is necessary for the optimal administration of anti-arrhythmic drugs in the treatment of heart arrhythmia. The present study aimed to develop and validate a direct analysis in real time tandem mass spectrometry (DART–MS/MS) method for the rapid and simultaneous determination of five anti-arrhythmic drugs (metoprolol, diltiazem, amiodarone, propafenone, and verapamil) and one metabolite (5-hydroxy(OH)-propafenone) in human serum. After the addition of isotope-labeled internal standards and protein precipitation with acetonitrile, anti-arrhythmic drugs were ionized by DART in positive mode followed by multiple reaction monitoring (MRM) detection. The use of DART–MS/MS avoided the need for chromatographic separation and allowed rapid and ultrahigh throughput analysis of anti-arrhythmic drugs in a total run time of 30 s per sample. The DART–MS/MS method yielded satisfactory linearity (R2 ≥ 0.9906), accuracy (86.1–109.9%), and precision (≤ 14.3%) with minimal effect of biological matrixes. The method was successfully applied to analyzing 30 clinical TDM samples. The relative error (RE) of the concentrations obtained by DART–MS/MS and liquid chromatography-tandem mass spectrometry (LC–MS/MS) was within ± 13%. This work highlights the potential usefulness of DART for the rapid quantitative analysis of anti-arrhythmic drugs in human serum and gives rapid feedback in the clinical TDM practices.https://doi.org/10.1038/s41598-020-72490-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuzhou Gui Youli Lu Shuijun Li Mengqi Zhang Xiaokun Duan Charles C. Liu Jingying Jia Gangyi Liu |
spellingShingle |
Yuzhou Gui Youli Lu Shuijun Li Mengqi Zhang Xiaokun Duan Charles C. Liu Jingying Jia Gangyi Liu Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring Scientific Reports |
author_facet |
Yuzhou Gui Youli Lu Shuijun Li Mengqi Zhang Xiaokun Duan Charles C. Liu Jingying Jia Gangyi Liu |
author_sort |
Yuzhou Gui |
title |
Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring |
title_short |
Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring |
title_full |
Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring |
title_fullStr |
Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring |
title_full_unstemmed |
Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring |
title_sort |
direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-09-01 |
description |
Abstract Therapeutic drug monitoring (TDM) is necessary for the optimal administration of anti-arrhythmic drugs in the treatment of heart arrhythmia. The present study aimed to develop and validate a direct analysis in real time tandem mass spectrometry (DART–MS/MS) method for the rapid and simultaneous determination of five anti-arrhythmic drugs (metoprolol, diltiazem, amiodarone, propafenone, and verapamil) and one metabolite (5-hydroxy(OH)-propafenone) in human serum. After the addition of isotope-labeled internal standards and protein precipitation with acetonitrile, anti-arrhythmic drugs were ionized by DART in positive mode followed by multiple reaction monitoring (MRM) detection. The use of DART–MS/MS avoided the need for chromatographic separation and allowed rapid and ultrahigh throughput analysis of anti-arrhythmic drugs in a total run time of 30 s per sample. The DART–MS/MS method yielded satisfactory linearity (R2 ≥ 0.9906), accuracy (86.1–109.9%), and precision (≤ 14.3%) with minimal effect of biological matrixes. The method was successfully applied to analyzing 30 clinical TDM samples. The relative error (RE) of the concentrations obtained by DART–MS/MS and liquid chromatography-tandem mass spectrometry (LC–MS/MS) was within ± 13%. This work highlights the potential usefulness of DART for the rapid quantitative analysis of anti-arrhythmic drugs in human serum and gives rapid feedback in the clinical TDM practices. |
url |
https://doi.org/10.1038/s41598-020-72490-w |
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