Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study
HCV-genotype-4 (HCV-GT4) is the cause of approximately 20% of the 170 million cases of chronic hepatitis C virus (HCV) in the world. Around 95% of patients with chronic HCV infection can be cure by utilizing direct-acting antiviral treatment. Two anti-HCV genotype 4 co-administered ravidasvir (RAV)...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-11-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535220303828 |
| _version_ | 1818251142340018176 |
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| author | Mohamed Hefnawy Sherif Hammad Adnan Kadi Nawaf Alsaif Mostafa Mohammed Abdullah Al-Hossaini Yousef Bin Jardan Mohamed Attwa Maha Abou-El-Alamin |
| author_facet | Mohamed Hefnawy Sherif Hammad Adnan Kadi Nawaf Alsaif Mostafa Mohammed Abdullah Al-Hossaini Yousef Bin Jardan Mohamed Attwa Maha Abou-El-Alamin |
| author_sort | Mohamed Hefnawy |
| collection | DOAJ |
| description | HCV-genotype-4 (HCV-GT4) is the cause of approximately 20% of the 170 million cases of chronic hepatitis C virus (HCV) in the world. Around 95% of patients with chronic HCV infection can be cure by utilizing direct-acting antiviral treatment. Two anti-HCV genotype 4 co-administered ravidasvir (RAV) and sofosbuvir (SOF) were simultaneously quantified in rat plasma by a validated and sensitive LC-MS/MS method using aciclovir as an internal standard. Chromatographic resolution for all analytes was performed with an Eclipse plus C18 column (50 mm × 2.1 mm, 1.8 µm) with isocratic mobile phase consisted of 10 mM ammonium formate: acetonitrile (61:39, v/v, pH 4.0) at a flow rate of 0.25 mL/min. Sample pre-treatment involved protein precipitation in plasma and stable internal standard resulted in a sensitive and robust method. Positive multiple reaction monitoring (MRM) mode was chosen to identify RAV, SOF, and IS. The developed assay was validated for accuracy, precision, linearity, selectivity, extraction recovery, matrix effect, carry-over, dilution integrity, and stability in accordance with US-FDA bioanalytical method validation guidelines. The method was linear over the ranges of 0.5–600 and 1–3000 ng/mL of RAV and SOF, respectively (r2 ≥ 0.997). After injection of the HLOQ sample, carry-over in the blank sample was less than 20% of the LLOQ of RAV, SOF and less than 5% of the IS. The mean relative standard deviation (RSD) of the results of accuracy and precision were ≤9.74%, and the overall recoveries of RAV and SOF from rat plasma were in the range 92.53–107.25%. The current methodology is the first LC-MS/MS for the quantification of RAV and SOF in rat plasma and to applied the pharmacokinetics of these agents in rats. |
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| id | doaj.art-8fdd15e9ec0543a6992993cec928addb |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-12-12T16:03:35Z |
| publishDate | 2020-11-01 |
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| series | Arabian Journal of Chemistry |
| spelling | doaj.art-8fdd15e9ec0543a6992993cec928addb2022-12-22T00:19:22ZengElsevierArabian Journal of Chemistry1878-53522020-11-01131181608171Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic studyMohamed Hefnawy0Sherif Hammad1Adnan Kadi2Nawaf Alsaif3Mostafa Mohammed4Abdullah Al-Hossaini5Yousef Bin Jardan6Mohamed Attwa7Maha Abou-El-Alamin8Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Corresponding author at: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, 11795 Cairo, Egypt; Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology (E-JUST), P.O. Box 179, New Borg El-Arab City, 21934 Alexandria, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; National Organization for Drug Control and Research, P.O. Box 29, Cairo, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Analytical Chemistry, Faculty of Pharmacy, Helwan University, 11795 Cairo, EgyptHCV-genotype-4 (HCV-GT4) is the cause of approximately 20% of the 170 million cases of chronic hepatitis C virus (HCV) in the world. Around 95% of patients with chronic HCV infection can be cure by utilizing direct-acting antiviral treatment. Two anti-HCV genotype 4 co-administered ravidasvir (RAV) and sofosbuvir (SOF) were simultaneously quantified in rat plasma by a validated and sensitive LC-MS/MS method using aciclovir as an internal standard. Chromatographic resolution for all analytes was performed with an Eclipse plus C18 column (50 mm × 2.1 mm, 1.8 µm) with isocratic mobile phase consisted of 10 mM ammonium formate: acetonitrile (61:39, v/v, pH 4.0) at a flow rate of 0.25 mL/min. Sample pre-treatment involved protein precipitation in plasma and stable internal standard resulted in a sensitive and robust method. Positive multiple reaction monitoring (MRM) mode was chosen to identify RAV, SOF, and IS. The developed assay was validated for accuracy, precision, linearity, selectivity, extraction recovery, matrix effect, carry-over, dilution integrity, and stability in accordance with US-FDA bioanalytical method validation guidelines. The method was linear over the ranges of 0.5–600 and 1–3000 ng/mL of RAV and SOF, respectively (r2 ≥ 0.997). After injection of the HLOQ sample, carry-over in the blank sample was less than 20% of the LLOQ of RAV, SOF and less than 5% of the IS. The mean relative standard deviation (RSD) of the results of accuracy and precision were ≤9.74%, and the overall recoveries of RAV and SOF from rat plasma were in the range 92.53–107.25%. The current methodology is the first LC-MS/MS for the quantification of RAV and SOF in rat plasma and to applied the pharmacokinetics of these agents in rats.http://www.sciencedirect.com/science/article/pii/S1878535220303828LC-MS/MSRavidasvirSofosbuvirRat plasmaPharmacokinetics |
| spellingShingle | Mohamed Hefnawy Sherif Hammad Adnan Kadi Nawaf Alsaif Mostafa Mohammed Abdullah Al-Hossaini Yousef Bin Jardan Mohamed Attwa Maha Abou-El-Alamin Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study Arabian Journal of Chemistry LC-MS/MS Ravidasvir Sofosbuvir Rat plasma Pharmacokinetics |
| title | Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study |
| title_full | Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study |
| title_fullStr | Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study |
| title_full_unstemmed | Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study |
| title_short | Effective quantification of ravidasvir (an NS5A inhibitor) and sofosbuvir in rat plasma by validated LC-MS/MS method and its application to pharmacokinetic study |
| title_sort | effective quantification of ravidasvir an ns5a inhibitor and sofosbuvir in rat plasma by validated lc ms ms method and its application to pharmacokinetic study |
| topic | LC-MS/MS Ravidasvir Sofosbuvir Rat plasma Pharmacokinetics |
| url | http://www.sciencedirect.com/science/article/pii/S1878535220303828 |
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