A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19

The combined prescriptions of nirmatrelvir/ritonavir and other drugs are limited due to potential drug-drug interactions, so therapeutic drug monitoring (TDM) becomes particularly important. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determi...

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Main Authors: Xiujing Zhu, Lin Li, Bing Dai, Zhijun Liu, Zhipeng Wang, Lili Cui, Shouhong Gao, Wansheng Chen, Xia Tao, Deduo Xu
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:International Journal of Analytical Chemistry
Online Access:http://dx.doi.org/10.1155/2024/6139928
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author Xiujing Zhu
Lin Li
Bing Dai
Zhijun Liu
Zhipeng Wang
Lili Cui
Shouhong Gao
Wansheng Chen
Xia Tao
Deduo Xu
author_facet Xiujing Zhu
Lin Li
Bing Dai
Zhijun Liu
Zhipeng Wang
Lili Cui
Shouhong Gao
Wansheng Chen
Xia Tao
Deduo Xu
author_sort Xiujing Zhu
collection DOAJ
description The combined prescriptions of nirmatrelvir/ritonavir and other drugs are limited due to potential drug-drug interactions, so therapeutic drug monitoring (TDM) becomes particularly important. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the nirmatrelvir/ritonavir in plasma of patients with COVID-19, providing technical and theoretical support for the TDM. Plasma samples were processed by protein precipitation using acetonitrile, and analytes were separated on an Agilent Poroshell 120 SB-C18 (2.1 × 75 mm, 2.7 μm) column at 35°C. Acetonitrile and 0.1% formic acid in water (52 : 48) were utilized as the mobile phases at a flow rate of 0.3 mL/min. In the multiple reaction monitoring (MRM) mode, nirmatrelvir and ritonavir were monitored using precursor/product ions: m/z 500.2/110.1 and 721.3/296.1, respectively, with selinexor as the internal standard. The linear range of both analytes was 2.0 ng/mL to 5000 ng/mL with good inter- and intraday precision and accuracy, and the recovery was 92.0%–107% for nirmatrelvir and 85.7%–106% for ritonavir. Finally, this method was successfully applied to monitor the exposure levels of nirmatrelvir/ritonavir in plasma samples from hemodialysis patients.
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spelling doaj-art-4ec970994fcd4cdabbe6e57249b4e4842025-08-20T02:05:35ZengWileyInternational Journal of Analytical Chemistry1687-87792024-01-01202410.1155/2024/6139928A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19Xiujing Zhu0Lin Li1Bing Dai2Zhijun Liu3Zhipeng Wang4Lili Cui5Shouhong Gao6Wansheng Chen7Xia Tao8Deduo Xu9Department of PharmacyDepartment of NephrologyDepartment of NephrologyDepartment of PharmacyDepartment of PharmacyDepartment of PharmacyDepartment of PharmacyDepartment of PharmacyDepartment of PharmacyDepartment of PharmacyThe combined prescriptions of nirmatrelvir/ritonavir and other drugs are limited due to potential drug-drug interactions, so therapeutic drug monitoring (TDM) becomes particularly important. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the nirmatrelvir/ritonavir in plasma of patients with COVID-19, providing technical and theoretical support for the TDM. Plasma samples were processed by protein precipitation using acetonitrile, and analytes were separated on an Agilent Poroshell 120 SB-C18 (2.1 × 75 mm, 2.7 μm) column at 35°C. Acetonitrile and 0.1% formic acid in water (52 : 48) were utilized as the mobile phases at a flow rate of 0.3 mL/min. In the multiple reaction monitoring (MRM) mode, nirmatrelvir and ritonavir were monitored using precursor/product ions: m/z 500.2/110.1 and 721.3/296.1, respectively, with selinexor as the internal standard. The linear range of both analytes was 2.0 ng/mL to 5000 ng/mL with good inter- and intraday precision and accuracy, and the recovery was 92.0%–107% for nirmatrelvir and 85.7%–106% for ritonavir. Finally, this method was successfully applied to monitor the exposure levels of nirmatrelvir/ritonavir in plasma samples from hemodialysis patients.http://dx.doi.org/10.1155/2024/6139928
spellingShingle Xiujing Zhu
Lin Li
Bing Dai
Zhijun Liu
Zhipeng Wang
Lili Cui
Shouhong Gao
Wansheng Chen
Xia Tao
Deduo Xu
A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19
International Journal of Analytical Chemistry
title A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19
title_full A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19
title_fullStr A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19
title_full_unstemmed A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19
title_short A Simple and Rapid LC-MS/MS Method for the Quantification of Nirmatrelvir/Ritonavir in Plasma of Patients with COVID-19
title_sort simple and rapid lc ms ms method for the quantification of nirmatrelvir ritonavir in plasma of patients with covid 19
url http://dx.doi.org/10.1155/2024/6139928
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