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Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19
Nirmatrelvir is an antiviral agent active against SARS-CoV-2, the virus causing the pandemic disease COVID-19. It is administrated in combination with the protease inhibitor ritonavir, which acts in case of COVID-19 mainly as enzyme blocking agent preventing the premature metabolic elimination of ni...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576249/ https://www.ncbi.nlm.nih.gov/pubmed/36274268 http://dx.doi.org/10.1016/j.jchromb.2022.123510 |
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author | Martens-Lobenhoffer, Jens Böger, Corinna R. Kielstein, Jan Bode-Böger, Stefanie M. |
author_facet | Martens-Lobenhoffer, Jens Böger, Corinna R. Kielstein, Jan Bode-Böger, Stefanie M. |
author_sort | Martens-Lobenhoffer, Jens |
collection | PubMed |
description | Nirmatrelvir is an antiviral agent active against SARS-CoV-2, the virus causing the pandemic disease COVID-19. It is administrated in combination with the protease inhibitor ritonavir, which acts in case of COVID-19 mainly as enzyme blocking agent preventing the premature metabolic elimination of nirmatrelvir. The combination of the two drugs in separate tablets is marketed under the brand name Paxlovid® and shows good effectivity in preventing the progression of COVID-19 to severe disease state. In this work, we described a LC-MS/MS method for the simultaneous quantification of nirmatrelvir and ritonavir in human plasma of patients treated for COVID-19 with Paxlovid®. After addition of D(6)-ritonavir as internal standard, plasma proteins were precipitated by the addition of methanol. The analytes were separated by gradient elution on a C18-column and were detected by tandem mass spectrometry. Calibration functions were linear in the ranges of 10 – 10000 ng/mL for nirmatrelvir and 2 – 2000 ng/mL for ritonavir. Inter-day and intra-day precision and accuracy was better than 15 % in the quality control samples and better than 20 % at the LLOQ. The method was successfully applied on samples of hospitalized patients treated for COVID-19 and proved to be capable in supporting therapeutic drug monitoring (TDM). |
format | Online Article Text |
id | pubmed-9576249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95762492022-10-18 Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19 Martens-Lobenhoffer, Jens Böger, Corinna R. Kielstein, Jan Bode-Böger, Stefanie M. J Chromatogr B Analyt Technol Biomed Life Sci Article Nirmatrelvir is an antiviral agent active against SARS-CoV-2, the virus causing the pandemic disease COVID-19. It is administrated in combination with the protease inhibitor ritonavir, which acts in case of COVID-19 mainly as enzyme blocking agent preventing the premature metabolic elimination of nirmatrelvir. The combination of the two drugs in separate tablets is marketed under the brand name Paxlovid® and shows good effectivity in preventing the progression of COVID-19 to severe disease state. In this work, we described a LC-MS/MS method for the simultaneous quantification of nirmatrelvir and ritonavir in human plasma of patients treated for COVID-19 with Paxlovid®. After addition of D(6)-ritonavir as internal standard, plasma proteins were precipitated by the addition of methanol. The analytes were separated by gradient elution on a C18-column and were detected by tandem mass spectrometry. Calibration functions were linear in the ranges of 10 – 10000 ng/mL for nirmatrelvir and 2 – 2000 ng/mL for ritonavir. Inter-day and intra-day precision and accuracy was better than 15 % in the quality control samples and better than 20 % at the LLOQ. The method was successfully applied on samples of hospitalized patients treated for COVID-19 and proved to be capable in supporting therapeutic drug monitoring (TDM). Elsevier B.V. 2022-12-01 2022-10-17 /pmc/articles/PMC9576249/ /pubmed/36274268 http://dx.doi.org/10.1016/j.jchromb.2022.123510 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Martens-Lobenhoffer, Jens Böger, Corinna R. Kielstein, Jan Bode-Böger, Stefanie M. Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19 |
title | Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19 |
title_full | Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19 |
title_fullStr | Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19 |
title_full_unstemmed | Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19 |
title_short | Simultaneous quantification of nirmatrelvir and ritonavir by LC-MS/MS in patients treated for COVID-19 |
title_sort | simultaneous quantification of nirmatrelvir and ritonavir by lc-ms/ms in patients treated for covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576249/ https://www.ncbi.nlm.nih.gov/pubmed/36274268 http://dx.doi.org/10.1016/j.jchromb.2022.123510 |
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