BİR İNFLUENZA VİRÜSÜ NÖRAMİNİDAZ İNHİBİTÖRÜ OLAN PERAMIVİR’İN SAPTANMASI İÇİN MOLEKÜLER BASKI POLİMER İLE ELEKTROKİMYASAL SENSÖRÜN GELİŞTİRİLMESİ

Year 2024, , 75 - 85, 20.01.2024

Göksu Özçelikay Akyıldız , Sibel A. Özkan

https://doi.org/10.33483/jfpau.1348090

Abstract

Amaç: Grip virüsleri, gribin en yaygın nedenidir. Antiviral ilaçlar virüsün enfekte hücreler yoluyla yayılmasını engeller. Peramivir, influenza virüsü nöraminidazının inhibitörü olan antiviral ilaçlardan biridir. Çalışmamızda Peramivir tayini için MIP tabanlı bir elektrokimyasal sensör geliştirilmesi amaçlanmıştır. Bu çalışma, Peramivir analizi için geliştirilen ilk elektrokimyasal sensör çalışmasıdır. MIP(PERA)/GCE, Peramivir varlığında 4-aminofenol (4-AP) ve ortofenilendiaminin (o-PD) monomerlerin elektropolimerizasyonu ile geliştirilmiştir. Geliştirilen MIP(PERA)/GCE, Peramivir analizi için ticari serum örneğine uygulanmıştır.
Gereç ve Yöntem: Peramivir, Tobio Novelpharma ilaç şirketi (İstanbul, Türkiye) tarafından sağlanmıştır. Potasyum ferrisiyanür ([K3Fe(CN)6]), potasyum ferrosiyanür (K4[Fe(CN)6].3H2O) potasyum klorür(KCl), 4-aminofenol (4-AP) ve ortofenilendiamin (o-PD), sentetik insan serumu, dopamin, askorbik asit, ürik asit, parasetamol, KNO3, Na2SO4 ve MgCl2 Sigma-Aldrich'ten (St. Louis, Missouri, ABD) temin edilmiştir. Metanol, asetik asit, okzalik asit, hidroklorik asit, asetonitril sodyum hidroksit ve etanol Merck tarafından tedarik edilmiştir. Redoks işlemi, Dropsens μStat 400 Bipotantiostat/ Galvanostat (Metrohm, Herisau, İsviçre) tarafından döngüsel voltametri (CV) ve diferansiyel puls voltammetrisi (DPV) kullanılarak gerçekleşmiştir. Üç elektrotlu sistemler, bir camsı karbon çalışma elektrodu (GCE, 3mm2, BASi, ABD), doymuş bir Ag/AgCl referans elektrodu ve bir Pt telinden oluşmuştur.
Sonuç ve Tartışma: Geliştirilen sensör, 0,158 pM en düşük tayin limiti ile 1-10 pM doğrusal bir aralık göstermiştir. Geliştirilen MIP sensörü ticari bir serum örneğine uygulanmıştır. MIP(PERA)/GCE sensörü ile %101.81'lik yüksek bir geri kazanımla ticari serum örneklerinden peramivir saptanmıştır.

Keywords

Elektrokimyasal sensör, miktar tayini, molekül baskılanmış polimer, peramivir, ticari serum örneği

DEVELOPMENT OF ELECTROCHEMICAL SENSOR BY MOLECULARLY IMPRINTING POLYMER FOR DETECTION OF AN INFLUENZA VIRUS NEURAMINIDASE INHIBITOR PERAMIVIR

Abstract

Objective: Influenza viruses are the most common cause of influenza. Antiviral drugs prevent the spread of the virus through the infected cells. Peramivir is one of the antiviral drugs that is an inhibitor of influenza virus neuraminidase. In our study, we aimed to develop a MIP-based electrochemical sensor to determine Peramivir. This study is the first to create an electrochemical sensor for Peramivir. MIP(PERA)/GCE was fabricated with the electropolymerization of 4-aminophenol (4-AP) and ortophenilendiamine (o-PD) in the presence of Peramivir. The developed MIP(PERA)/GCE was applied to the commercial serum sample for analysis of Peramivir.
Material and Method: PERA is supplied by Tobio Novelpharma pharmaceutical company (İstanbul, Türkiye). Potassium ferricyanide ([K3Fe(CN)6]), potassium ferrocyanide (K4[Fe(CN)6].3H2O), and potassium chloride (KCl), 4-aminophenol (4-AP) and ortophenilendiamine (o-PD), commercial human serum sample, dopamine, ascorbic acid, uric acid, paracetamol, KNO3, Na2SO4 ve MgCl2 were obtained from Sigma-Aldrich (St. Louis, Missouri, USA). Methanol, acetic acid, oxalic acid, hydrochloric acid, acetonitrile, sodium hydroxide, and ethanol were purchased by Merck. The redox process was investigated using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) by the Dropsens μStat 400 Bipotantiostat/ Galvanostat (Metrohm, Herisau, Switzerland). Three-electrode systems consisted of a glassy carbon working electrode (GCE, 3mm2, BASi, USA), a saturated Ag/AgCl reference electrode, and a Pt wire.
Result and Discussion: The sensor exhibits a linear range of 1-10 pM with a detection limit of 0.158 pM. The MIP(PERA)/GCE sensor could detect PERA from commercial serum samples with a high recovery of 101.81%.

Keywords

Commercial serum sample, determination, electrochemical sensor, molecularly imprinted polymer, peramivir

References

• 1. Atkins, C., Evans, C.W., White, E.L., Noah, J.W. (2012). Screening methods for influenza antiviral drug discovery. Expert Opinion on Drug Discovery, 7(5), 429-438. [CrossRef]
• 2. Mikurova, A.V., Skvortsov, V.S. (2018). A generalized prediction model of inhibition of neuraminidase of influenza virus of various strains. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 12(4), 322-329. [CrossRef]
• 3. Lingabathula, S., Jain, N. (2021). Stability indicative and cost effective analytical method development and validation of favipiravir and peramivir in bulk and pharmaceutical dosage form by using RP-HPLC. International Journal of Applied Pharmaceutics, 13(4), 265-271. [CrossRef]
• 4. Lei, M., Gan, W., Sun, Y. (2018). HPLC-MS/MS analysis of peramivir in rat plasma: Elimination of matrix effect using the phospholipid-removal solid-phase extraction method. Biomedical Chromatography, 32(3),e4103. [CrossRef]
• 5. Li, X., Li, Y., Wang, J., Wang, L., Zhong, W., Ruan, J., Zhang, Z. (2014). Quantification of peramivir in dog plasma by liquid chromatography/tandem mass spectrometry employing precolumn derivatization. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 944(1), 1-5. [CrossRef]
• 6. Lindegardh, N., Hanpithakpong, W., Phakdeeraj, A., Singhasivanon, P., Farrar, J., Hien, T.T., White, N.J., Day, N.P.J. (2008). Development and validation of a high-throughput zwitterionic hydrophilic interaction liquid chromatography solid-phase extraction-liquid chromatography-tandem mass spectrometry method for determination of the anti-influenza drug peramivir in plasma. Journal of Chromatography A, 1215(1-2), 145-151. [CrossRef]
• 7. Ozkan, S.A., Kauffmann, J.M., Zuman, P. (2015b). Electroanalytical method validation in pharmaceutical Analysis and Their Applications. Springer, Berlin, Heidelberg. (235-266). [CrossRef]
• 8. Mattiasson, B. Erturk, G. (2017). Why using molecularly imprinted polymers in connection to biosensors. In Biosensors and Molecular Imprinting. 17(2), 246. [CrossRef]
• 9. Spégel, P., Schweitz, L., Nilsson, S. (2002). Molecularly imprinted polymers. Analytical and Bioanalytical Chemistry, 372(1), 37-38. [CrossRef]
• 10. Kaya, S.I., Corman, M.E., Uzun, L., Ozkan, S.A. (2022). Simple preparation of surface molecularly imprinted polymer based on silica particles for trace level assay of bisphenol F. Analytical and Bioanalytical Chemistry, 414(19), 5793-5803. [CrossRef]
• 11. Cetinkaya, A., Kaya, S.I., Atici, E.B., Çorman, M.E., Uzun, L., Ozkan, S.A. (2022). A semi-covalent molecularly imprinted electrochemical sensor for rapid and selective detection of tiotropium bromide. Analytical and Bioanalytical Chemistry, 414, 8023-8033. [CrossRef]
• 12. Çorman, M.E., Cetinkaya, A., Armutcu, C., Bellur Atici, E., Uzun, L., Ozkan, S.A. (2022). A sensitive and selective electrochemical sensor based on molecularly imprinted polymer for the assay of teriflunomide. Talanta, 249, 123689. [CrossRef]
• 13. Kaya, S.I., Cetinkaya, A., Atici, E.B., Çorman, M.E., Uzun, L., Ozkan, S.A. (2023). Electrochemical sensing of aclidinium bromide with metal ion-assisted molecularly imprinted films. Microchemical Journal, 184, 108128. [CrossRef]
• 14. Ozcelikay, G., Kaya, S.I., Ozkan, E., Cetinkaya, A., Nemutlu, E., Kır, S., Ozkan, S.A. (2022). Sensor-based MIP technologies for targeted metabolomics analysis. TrAC. Trends in Analytical Chemistry, 146, 116487. [CrossRef]
• 15. Ozcelikay, G., Kurbanoglu, S., Zhang, X., Soz, C.K., Wollenberger, U., Ozkan, S.A., Yarman, A., Scheller, F.W. (2019). Electrochemical MIP sensor for butyrylcholinesterase. Polymers, 11(12), 1-11. [CrossRef]
• 16. Piletsky, S.A., Turner, A.P.F. (2002). Electrochemical sensors based on molecularly imprinted polymers. Electroanalysis, 14(5), 317-323. [CrossRef]
• 17. Ramanavicius, S., Jagminas, A., Ramanavicius, A. (2021). Advances in molecularly imprinted polymers based affinity sensors (review). Polymers, 13(6), 974. [CrossRef]
• 18. Ozcelikay, G., Karadas-Bakirhan, N., Taskin-Tok, T., Ozkan, S.A. (2020). A selective and molecular imaging approach for anticancer drug: Pemetrexed by nanoparticle accelerated molecularly imprinting polymer. Electrochimica Acta, 354, 136665. [CrossRef]
• 19. Ich Harmonised Tripartite Guideline. (1996). Guidance for industry Q2B validation of analytical procedures: methodology. 20857(November), 301-827.
• 20. Ozkan, S.A., Kauffmann, J.M., Zuman, P. (2015a). Electroanalysis in Biomedical and Pharmaceutical Sciences, Springer Berlin, Heidelberg, p. 350 [CrossRef]