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A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies

Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxy...

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Autores principales: Reçber, Tuba, Timur, Selin Seda, Erdoğan Kablan, Sevilay, Yalçın, Fatma, Karabulut, Tutku Ceren, Neslihan Gürsoy, R., Eroğlu, Hakan, Kır, Sedef, Nemutlu, Emirhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881887/
https://www.ncbi.nlm.nih.gov/pubmed/35276385
http://dx.doi.org/10.1016/j.jpba.2022.114693
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author Reçber, Tuba
Timur, Selin Seda
Erdoğan Kablan, Sevilay
Yalçın, Fatma
Karabulut, Tutku Ceren
Neslihan Gürsoy, R.
Eroğlu, Hakan
Kır, Sedef
Nemutlu, Emirhan
author_facet Reçber, Tuba
Timur, Selin Seda
Erdoğan Kablan, Sevilay
Yalçın, Fatma
Karabulut, Tutku Ceren
Neslihan Gürsoy, R.
Eroğlu, Hakan
Kır, Sedef
Nemutlu, Emirhan
author_sort Reçber, Tuba
collection PubMed
description Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, is one of the promising candidates for SARS-CoV-2 treatment. In this study, a RP-HPLC method was developed for the determination of Molnupiravir and applied for in vitro permeability studies of self-emulsifying drug delivery system (SEDDS) formulations using Caco-2 cell line. Discovery® HS C18 Column (75 ×4.6 mm, 3 µm) was used at 30 °C. Isocratic elution was performed with ACN:water (20:80 v/v) mixture. The flow rate was 0.5 mL/min and UV detection was at 240 nm. Molnupiravir eluted within 5 min. Molnupiravir was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions. Peak homogeneity data of Molnupiravir in the stressed samples peak obtained using photodiode array detector, in the stressed sample chromatograms, demonstrated the specificity of the method for their estimation in presence of degradants. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines and found to be linear within the range 0.1–60.0 μg/mL. The method was simple, rapid, selective, sensitive, accurate, precise, robust and rugged. Thus, it was applied successfully for permeability quantitation of Molnupiravir in nanoformulations. The apparent permeability of Molnupiravir in SEDDS formulations, which have droplet size under 350 nm, was calculated as 3.20 ± 0.44 × 10(−6) cm/s.
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spelling pubmed-88818872022-02-28 A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies Reçber, Tuba Timur, Selin Seda Erdoğan Kablan, Sevilay Yalçın, Fatma Karabulut, Tutku Ceren Neslihan Gürsoy, R. Eroğlu, Hakan Kır, Sedef Nemutlu, Emirhan J Pharm Biomed Anal Article Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, is one of the promising candidates for SARS-CoV-2 treatment. In this study, a RP-HPLC method was developed for the determination of Molnupiravir and applied for in vitro permeability studies of self-emulsifying drug delivery system (SEDDS) formulations using Caco-2 cell line. Discovery® HS C18 Column (75 ×4.6 mm, 3 µm) was used at 30 °C. Isocratic elution was performed with ACN:water (20:80 v/v) mixture. The flow rate was 0.5 mL/min and UV detection was at 240 nm. Molnupiravir eluted within 5 min. Molnupiravir was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions. Peak homogeneity data of Molnupiravir in the stressed samples peak obtained using photodiode array detector, in the stressed sample chromatograms, demonstrated the specificity of the method for their estimation in presence of degradants. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines and found to be linear within the range 0.1–60.0 μg/mL. The method was simple, rapid, selective, sensitive, accurate, precise, robust and rugged. Thus, it was applied successfully for permeability quantitation of Molnupiravir in nanoformulations. The apparent permeability of Molnupiravir in SEDDS formulations, which have droplet size under 350 nm, was calculated as 3.20 ± 0.44 × 10(−6) cm/s. Elsevier B.V. 2022-05-30 2022-02-26 /pmc/articles/PMC8881887/ /pubmed/35276385 http://dx.doi.org/10.1016/j.jpba.2022.114693 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
Reçber, Tuba
Timur, Selin Seda
Erdoğan Kablan, Sevilay
Yalçın, Fatma
Karabulut, Tutku Ceren
Neslihan Gürsoy, R.
Eroğlu, Hakan
Kır, Sedef
Nemutlu, Emirhan
A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies
title A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies
title_full A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies
title_fullStr A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies
title_full_unstemmed A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies
title_short A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies
title_sort stability indicating rp-hplc method for determination of the covid-19 drug molnupiravir applied using nanoformulations in permeability studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881887/
https://www.ncbi.nlm.nih.gov/pubmed/35276385
http://dx.doi.org/10.1016/j.jpba.2022.114693
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