Rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS

Objectives: There is no analytical method for simultaneous monitoring of warfarin and novel direct oral anticoagulants (NOACs) in human urine samples in a single run in the clinics. Although several studies have reported their measurements in human blood samples, but its sample collection is more in...

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Autores principales: Tzu-Yu Pan, Wei-Chung Tsai, Chun-Hsiang Tan, Ching-Mei Cheng, Wei Chen, Thiagarajan Soundappan, Mariadhas Valan Arasu, Naif Abdullah Al-Dhabi, Chia-Fang Wu, Vinoth Kumar Ponnusamy, Ming-Tsang Wu
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Publicado: Elsevier 2021
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spelling oai:doaj.org-article:7c4917bde92c4ec8a008ce4906bb281a2021-11-18T04:43:58ZRapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS1018-364710.1016/j.jksus.2021.101602https://doaj.org/article/7c4917bde92c4ec8a008ce4906bb281a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1018364721002640https://doaj.org/toc/1018-3647Objectives: There is no analytical method for simultaneous monitoring of warfarin and novel direct oral anticoagulants (NOACs) in human urine samples in a single run in the clinics. Although several studies have reported their measurements in human blood samples, but its sample collection is more invasive and time-consuming, thereby challenging to monitor frequently. Methods: In this work, we developed a fast microextraction technique (ultrasound-assisted salt-induced liquid-liquid microextraction, USA-SI-LLME) coupled with high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) to rapidly quantify four commonly used NOACs drugs (apixaban, dabigatran, edoxaban, and rivaroxaban) and warfarin in human urine samples. USA-SI-LLME conditions were optimized using a water-miscible organic solvent as an extraction solvent, high salt concentrations, sample pH, and extraction time (∼5.5 min). Results and conclusions: The analytical method showed excellent linearities from 0.5 to 500 μg/L for apixaban, edoxaban, rivaroxaban, warfarin, and 1 ∼ 500 μg/L for dabigatran. Intra- and inter-day precision values were <9.31% and R2 > 0.99 for all analytes. Limits of detection ranged between 0.07 ∼ 0.18 μg/L, and relative recoveries ranged between 92.18 and 110.15%. This method was successfully applied to analyze 15 one-spot urine samples from 15 clinical patients who regularly took warfarin or NOACs, and high accuracy was found. We concluded that this method could be used as a non-invasive high-throughput and rapid monitoring of NOACs and warfarin in human urine in clinical settings and could provide timely analysis during emergency care.Tzu-Yu PanWei-Chung TsaiChun-Hsiang TanChing-Mei ChengWei ChenThiagarajan SoundappanMariadhas Valan ArasuNaif Abdullah Al-DhabiChia-Fang WuVinoth Kumar PonnusamyMing-Tsang WuElsevierarticleNovel direct oral anticoagulantsWarfarinMicroextraction techniqueHuman urineLiquid chromatography–tandem mass spectrometryScience (General)Q1-390ENJournal of King Saud University: Science, Vol 33, Iss 8, Pp 101602- (2021)
institution DOAJ
collection DOAJ
language EN
topic Novel direct oral anticoagulants
Warfarin
Microextraction technique
Human urine
Liquid chromatography–tandem mass spectrometry
Science (General)
Q1-390
spellingShingle Novel direct oral anticoagulants
Warfarin
Microextraction technique
Human urine
Liquid chromatography–tandem mass spectrometry
Science (General)
Q1-390
Tzu-Yu Pan
Wei-Chung Tsai
Chun-Hsiang Tan
Ching-Mei Cheng
Wei Chen
Thiagarajan Soundappan
Mariadhas Valan Arasu
Naif Abdullah Al-Dhabi
Chia-Fang Wu
Vinoth Kumar Ponnusamy
Ming-Tsang Wu
Rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS
description Objectives: There is no analytical method for simultaneous monitoring of warfarin and novel direct oral anticoagulants (NOACs) in human urine samples in a single run in the clinics. Although several studies have reported their measurements in human blood samples, but its sample collection is more invasive and time-consuming, thereby challenging to monitor frequently. Methods: In this work, we developed a fast microextraction technique (ultrasound-assisted salt-induced liquid-liquid microextraction, USA-SI-LLME) coupled with high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) to rapidly quantify four commonly used NOACs drugs (apixaban, dabigatran, edoxaban, and rivaroxaban) and warfarin in human urine samples. USA-SI-LLME conditions were optimized using a water-miscible organic solvent as an extraction solvent, high salt concentrations, sample pH, and extraction time (∼5.5 min). Results and conclusions: The analytical method showed excellent linearities from 0.5 to 500 μg/L for apixaban, edoxaban, rivaroxaban, warfarin, and 1 ∼ 500 μg/L for dabigatran. Intra- and inter-day precision values were <9.31% and R2 > 0.99 for all analytes. Limits of detection ranged between 0.07 ∼ 0.18 μg/L, and relative recoveries ranged between 92.18 and 110.15%. This method was successfully applied to analyze 15 one-spot urine samples from 15 clinical patients who regularly took warfarin or NOACs, and high accuracy was found. We concluded that this method could be used as a non-invasive high-throughput and rapid monitoring of NOACs and warfarin in human urine in clinical settings and could provide timely analysis during emergency care.
format article
author Tzu-Yu Pan
Wei-Chung Tsai
Chun-Hsiang Tan
Ching-Mei Cheng
Wei Chen
Thiagarajan Soundappan
Mariadhas Valan Arasu
Naif Abdullah Al-Dhabi
Chia-Fang Wu
Vinoth Kumar Ponnusamy
Ming-Tsang Wu
author_facet Tzu-Yu Pan
Wei-Chung Tsai
Chun-Hsiang Tan
Ching-Mei Cheng
Wei Chen
Thiagarajan Soundappan
Mariadhas Valan Arasu
Naif Abdullah Al-Dhabi
Chia-Fang Wu
Vinoth Kumar Ponnusamy
Ming-Tsang Wu
author_sort Tzu-Yu Pan
title Rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS
title_short Rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS
title_full Rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS
title_fullStr Rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS
title_full_unstemmed Rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with LC–MS/MS
title_sort rapid simultaneous clinical monitoring of five oral anti-coagulant drugs in human urine using green microextraction technique coupled with lc–ms/ms
publisher Elsevier
publishDate 2021
url https://doaj.org/article/7c4917bde92c4ec8a008ce4906bb281a
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