Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MS
Introduction. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus (severe acute respiratory syndrome-related coronavirus 2). COVID-19 is now expected to stay with us for many years as a recurring disease. Molnupiravir and favipiravir are oral antiviral drugs w...
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| Format: | Article |
| Language: | Russian |
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LLC Center of Pharmaceutical Analytics (LLC «CPHA»)
2023-02-01
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| Series: | Разработка и регистрация лекарственных средств |
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| Online Access: | https://www.pharmjournal.ru/jour/article/view/1452 |
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| author | T. N. Komarov P. K. Karnakova O. A. Archakova D. S. Shchelgacheva N. S. Bagaeva I. E. Shohin K. Ya. Zaslavskaya P. A. Bely |
| author_facet | T. N. Komarov P. K. Karnakova O. A. Archakova D. S. Shchelgacheva N. S. Bagaeva I. E. Shohin K. Ya. Zaslavskaya P. A. Bely |
| author_sort | T. N. Komarov |
| collection | DOAJ |
| description | Introduction. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus (severe acute respiratory syndrome-related coronavirus 2). COVID-19 is now expected to stay with us for many years as a recurring disease. Molnupiravir and favipiravir are oral antiviral drugs with anti-RNA polymerase activity. The Russian Health Ministry has approved molnupiravir and favipiravir for the treatment of COVID-19. The study describes development and validation of high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of β-D-N4-Hydroxycytidine and favipiravir in human blood plasma. The method could be applied in pharmacokinetic study of molnupiravir and favipiravir.Aim. The aim of this study is to develop and validate a HPLC-MS/MS bioanalytical method for the determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma.Materials and methods. The determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma by HPLC-MS/MS. The samples were processed by 0.1 % formic acid in acetonitrile. Internal standard: promethazine. Mobile phase: 0.01 mol/L Ammonium formate buffer solution (Eluent A), 0.1 % formic acid and 0.08 % aqueous ammonia in water/acetonitrile 10 : 90 (Eluent B). Column: Shim-pack GWS C18, 150 × 4.6 mm, 5 μm. Analytical range: 50.00–10000.00 ng/mL for β-D-N4-Hydroxycytidine, 250.00–20000.00 ng/mL for favipiravir in human plasma. Ionization source: electrospray ionization. Detection conditions: 260.00 m/z → 82.10 m/z, 260.00 m/z → 111.00 m/z, 260.00 m/z → 127.95 m/z (β-D-N4-Hydroxycytidine); 156.15 m/z → 65.95 m/z, 156.15 m/z → 85.00 m/z, 156.15 m/z → 113.10 m/z (favipiravir); 285.05 m/z → 198.05 m/z (promethazine).Results and discussion. This method was validated by selectivity, suitability of reference standard, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability.Conclusion. The HPLC-MS/MS method for quantitative determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma was developed and validated. The analytical range was 50.00–10000.00 ng/mL for β-D-N4-Hydroxycytidine, 250.00–20000.00 ng/mL for favipiravir in human plasma. This method was applied to investigate the pharmacokinetics of molnupiravir and favipiravir. |
| format | Article |
| id | doaj-art-238ed64bf7414d6a853f1bf6f03ebcc2 |
| institution | Kabale University |
| issn | 2305-2066 2658-5049 |
| language | Russian |
| publishDate | 2023-02-01 |
| publisher | LLC Center of Pharmaceutical Analytics (LLC «CPHA») |
| record_format | Article |
| series | Разработка и регистрация лекарственных средств |
| spelling | doaj-art-238ed64bf7414d6a853f1bf6f03ebcc22025-08-20T03:39:45ZrusLLC Center of Pharmaceutical Analytics (LLC «CPHA»)Разработка и регистрация лекарственных средств2305-20662658-50492023-02-0112121522610.33380/2305-2066-2023-12-1-215-2261089Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MST. N. Komarov0P. K. Karnakova1O. A. Archakova2D. S. Shchelgacheva3N. S. Bagaeva4I. E. Shohin5K. Ya. Zaslavskaya6P. A. Bely7LLC "CPHA"LLC "CPHA"LLC "CPHA"LLC "CPHA"LLC "CPHA"LLC "CPHA"LLC "PROMOMED RUS"LLC "PROMOMED RUS"Introduction. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus (severe acute respiratory syndrome-related coronavirus 2). COVID-19 is now expected to stay with us for many years as a recurring disease. Molnupiravir and favipiravir are oral antiviral drugs with anti-RNA polymerase activity. The Russian Health Ministry has approved molnupiravir and favipiravir for the treatment of COVID-19. The study describes development and validation of high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of β-D-N4-Hydroxycytidine and favipiravir in human blood plasma. The method could be applied in pharmacokinetic study of molnupiravir and favipiravir.Aim. The aim of this study is to develop and validate a HPLC-MS/MS bioanalytical method for the determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma.Materials and methods. The determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma by HPLC-MS/MS. The samples were processed by 0.1 % formic acid in acetonitrile. Internal standard: promethazine. Mobile phase: 0.01 mol/L Ammonium formate buffer solution (Eluent A), 0.1 % formic acid and 0.08 % aqueous ammonia in water/acetonitrile 10 : 90 (Eluent B). Column: Shim-pack GWS C18, 150 × 4.6 mm, 5 μm. Analytical range: 50.00–10000.00 ng/mL for β-D-N4-Hydroxycytidine, 250.00–20000.00 ng/mL for favipiravir in human plasma. Ionization source: electrospray ionization. Detection conditions: 260.00 m/z → 82.10 m/z, 260.00 m/z → 111.00 m/z, 260.00 m/z → 127.95 m/z (β-D-N4-Hydroxycytidine); 156.15 m/z → 65.95 m/z, 156.15 m/z → 85.00 m/z, 156.15 m/z → 113.10 m/z (favipiravir); 285.05 m/z → 198.05 m/z (promethazine).Results and discussion. This method was validated by selectivity, suitability of reference standard, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability.Conclusion. The HPLC-MS/MS method for quantitative determination of β-D-N4-Hydroxycytidine and favipiravir in human plasma was developed and validated. The analytical range was 50.00–10000.00 ng/mL for β-D-N4-Hydroxycytidine, 250.00–20000.00 ng/mL for favipiravir in human plasma. This method was applied to investigate the pharmacokinetics of molnupiravir and favipiravir.https://www.pharmjournal.ru/jour/article/view/1452β-d-n4-hydroxycytidinenhcmolnupiravirfavipiravircovid-19plasmahplc-ms/msvalidationpharmacokinetics |
| spellingShingle | T. N. Komarov P. K. Karnakova O. A. Archakova D. S. Shchelgacheva N. S. Bagaeva I. E. Shohin K. Ya. Zaslavskaya P. A. Bely Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MS Разработка и регистрация лекарственных средств β-d-n4-hydroxycytidine nhc molnupiravir favipiravir covid-19 plasma hplc-ms/ms validation pharmacokinetics |
| title | Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MS |
| title_full | Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MS |
| title_fullStr | Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MS |
| title_full_unstemmed | Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MS |
| title_short | Simultaneous Determination of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) and Favipiravir in Human Plasma by HPLC-MS/MS |
| title_sort | simultaneous determination of major molnupiravir metabolite β d n4 hydroxycytidine and favipiravir in human plasma by hplc ms ms |
| topic | β-d-n4-hydroxycytidine nhc molnupiravir favipiravir covid-19 plasma hplc-ms/ms validation pharmacokinetics |
| url | https://www.pharmjournal.ru/jour/article/view/1452 |
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