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...

Full description

Bibliographic Details
Main Authors: Yuzhou Gui, Youli Lu, Shuijun Li, Mengqi Zhang, Xiaokun Duan, Charles C. Liu, Jingying Jia, Gangyi Liu
Format: Article
Language:English
Published: Nature Publishing Group 2020-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-72490-w
id doaj-385224b5c9f14bb1bbfb7fe826e73ea5
record_format Article
spelling 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
work_keys_str_mv AT yuzhougui directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
AT youlilu directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
AT shuijunli directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
AT mengqizhang directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
AT xiaokunduan directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
AT charlescliu directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
AT jingyingjia directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
AT gangyiliu directanalysisinrealtimemassspectrometryforrapidquantificationoffiveantiarrhythmicdrugsinhumanserumapplicationtotherapeuticdrugmonitoring
_version_ 1716868000108249088