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Determination of Thermodynamic Protonation Constants of Some Selective Serotonin Reuptake Inhibitors in Water-Acetonitrile Binary Mixtures

Yıl 2022, Cilt: 22 Sayı: 5, 979 - 988, 27.10.2022
https://doi.org/10.35414/akufemubid.1126047

Öz

In this study, the retention behaviour of citalopram, fluvoxamine, and sertraline, selective serotonin reuptake inhibitors (SSRIs) used as alternatives to tricyclic antidepressants, was investigated in a binary water-acetonitrile mixture by reverse-phase liquid chromatographic (RPLC) method. Chromatographic analyzes were performed in binary acetonitrile-water mixtures with mobile phase pH ranging from 6.5 to 10.5 and acetonitrile content between 45% and 55% (v/v). Throughout the study, the column temperature and flow rate were fixed at 30 °C and 0.8 mL/min, respectively. In this study, the theoretical retention values were calculated by evaluating the retention values of the compounds against the pH values of the mobile phase using the linear solvation energy relationship (LSER) approach. In addition, the thermodynamic protonation constants ((_s^s)〖pK〗_a) of the compounds were determined with a nonlinear regression program, considering the activity coefficients of the mobile phases at different pH values. Using the (_s^s)〖pK〗_a values of the hydrophobic compounds, the values of the protonation constants in the water medium were calculated using two different approaches. At the end of the study, it was found that the results obtained by both extrapolation methods were compatible with each other.

Kaynakça

  • Aronson, J.K., 2016. Meyler’s Side Effects of Drugs. Elsevier, 250-340.
  • Avdeef, A., Sun, N., 2011. A New in situ brain perfusion flow correction method for lipophilic drugs based on the pH-dependent crone-renkin equation. Pharmacological Research, 28, 517–530.
  • Barbosa, J., Barrón, D., Jiménez-Lozano, E., Sanz-Nebot, V., 2001. Comparison between capillary electrophoresis, liquid chromatography, potentiometric and spectrophotometric techniques for evaluation of pKa values of zwitterionic drugs in acetonitrile–water mixtures. Analytica Chimica Acta, 437, 309–321.
  • Barbosa, J., Sanz-Nebot, V., Toro, I., 1996. Solvatochromic parameter values and pH in acetonitrile-water mixtures Optimization of mobile phase for the separation of peptides by high-performance liquid chromatography . Journal of Chromatography A, 725, 249-260.
  • Beltran, J.L., Sanli, N., Fonrodona, G., Barrón, D., Ozkan, G., Barbosa, J., 2003. Spectrophotometric, potentiometric and chromatographic pKa values of polyphenolic substances in water and acetonitrile-water media. Analytica Chimica Acta, 484, 253–264.
  • Bermel, R.A., Hashmonay, R., Meng, X., Randhawa, S., von Rosenstiel, P., Sfikas, N., Kantor, D., 2015. Fingolimod first-doseeffectsinpatients with relapsing multiplesclerosis concomitantly receiving selective serotonin-reuptakeinhibitors. Multiple Sclerosis and Related Disorders, 4, 273–280.
  • Daldal, Y.D., Çakır, C., Yılmaz, H., Demiralay, E.Ç., Özkan, S.A., Alsancak, G., 2014. Liquid Chromatographic, Spectrophotometric and Potentiometric pKa Determination of Ranitidine and Famotidine. Current Drug Therapy, 9, 277-284.
  • Daldal, Y.D., Demiralay, E.Ç., 2022. Development of liquid chromatographic and UV-visible spectrophotometric methods for determination of pKa values of folic acid antimetabolites. Journal of Pharmaceutical and Biomedical Analysis, 212, 1-8.
  • Deák, K., Takács-Novák, K., Tihanyi, K., Béla, N., 2006. Physico-Chemical profiling of antidepressive sertraline: solubility, ionisation, lipophilicity. Medicinal Chemistry, 2,1-6.
  • Herrero-Martínez, J., M., Repollés, C., Bosch, E., Rosés, M., Ràfols, C., 2008. Potentiometric determination of aqueous dissociation constants of flavonols sparingly soluble in water. Talanta, 74, 1008–1013.
  • Hoirisch-Clapauch, S., Nardi, A.E., Gris, J., Brenner, B., 2014. Are the antiplatelet and profibrinolytic properties of selective serotonin-reuptake inhibitors relevant to their brain effects?. Thrombosis Research, 134, 11–16.
  • Jacobsen, N.W., Hansen, C.H., Nellemann, C., Styrishave, B., Halling-Sørensen, B., 2015. Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicology in Vitro, 29, 1729–1735.
  • Kazakevich, Y., Lobrutto, Y., 2007. HPLC for Pharmaceutical Scientists. Wiley-Interscience, 139-249.
  • Li, J., 2002. P rediction of internal standards in reversed-phase liquid chromatography III. Evaluation of an alternative solvation parameter model to correlate and predict the retention of ionizable compounds. Journal of Chromatography A, 982, 209–223.
  • Luan, F., Ma, W., Zhang, H., Zhang, X., Liu, M., Hu, Z., Fan, B., 2005. Prediction of pKa for Neutral and Basic Drugs Based on Radial Basis Function Neural Networks and the Heuristic Method. Pharmaceutical Research, 22(9), 1454-1460.
  • Lunn, G., 2005. HPLC Methods For Recently Approved Pharmaceuticals. John Wiley and Sons, 38-387.
  • Meyer, V.R., 2010. Practical High-Performance Liquid Chromatography. John Wiley and Sons, 5-55.
  • Miguel, L., Barbas, C., 2003. LC determination of impurities in azithromycin tablets. Journal of Pharmaceutical and Biomedical Analysis, 33(2), 211–217.
  • Nane, I.D., Demiralay, E.C., 2021. Thermodynamic protonation constant values of meclizine and buclizine in acetonitrile-water binary mixtures, Journal of Research in Pharmacy, 25(1) , 42–51.
  • Nikitas, P., Pappa-Louisi, A., Agrafiotou, P., 2002. Effect of the organic modifier concentration on the retention in reversed-phase liquid chromatography II. Tests using various simplified models. Journal of chromatography A, 946(1–2), (2002) 33–45.
  • Ortak, H.Y., Demiralay, E.C., 2019. Effect of temperature on the retention of Janus kinase 3 inhibitor in different mobile phase compositions using reversed-phase liquid chromatography, Journal of Pharmaceutical and Biomedical Analysis, 164, 706–712.
  • Rondinini, S., Mussini, P.R., Mussini, T., 1987. Reference value standard and primary standard for pH measurements in organic solvents and water–organic solvent mixtures of moderate to high permittivities. Pure and Applied Chemistry, 59, 1549–1560.
  • Sun, N., Avdeef, A., 2011. Biorelevant pKa (37°C) predicted from the 2D structure of the molecule and its pKa at 25°C. Journal of Pharmaceutical and Biomedical Analysis, 56(2), 173–182.
  • Völgyi, G., Ruiz, R., Box, K., Comer, J., Bosch, E., Takács-Novák, K., 2007. Potentiometric and spectrophotometric pKa determination of water-insoluble compounds: Validation study in a new cosolvent system. Analytica Chimica Acta, 583, 418–428.
  • Volná, T., Motyka, K., Hlaváč, J., 2017. RP-HPLC determination of dissociation constant using solely aqueous mobile phase. Journal of Pharmaceutical and Biomedical Analysis,134, 143–148.
  • Yıldız, A., Genç, Ö., Bektaş, S., 1997. Enstrümental Analiz Yöntemleri. Hacettepe Üniversitesi Yayınları, 321-322.
  • İnternet Kaynakları 1- http://www.chemicalize.org, (01.06.2022)

Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi

Yıl 2022, Cilt: 22 Sayı: 5, 979 - 988, 27.10.2022
https://doi.org/10.35414/akufemubid.1126047

Öz

Bu çalışmada, trisiklik antidepresanlara alternatif olarak kullanılan selektif serotonin geri alım inhibitörleri (SSRİ)’nden sitalopram, fluvoksamin ve sertralinin su-asetonitril ikili karışımında, ters faz sıvı kromatografik (RPLC) yöntemle alıkonma davranışı incelenmiştir. Kromatografik analizler, mobil faz pH’sı 6,5 ila 10,5 arasında değişen, %45-%55 (h/h) arasında asetonitril içeren asetonitril-su ikili karışımlarında gerçekleştirilmiştir. Çalışma boyunca, kolon sıcaklığı ve akış hızı sırasıyla, 30 oC ve 0,8 mL/dakika’da sabitlenmiştir. Bu çalışmada, mobil faz pH değerlerine karşı bileşiklerin alıkonma değerlerinin lineer solvasyon enerjisi ilişkisi (LSER) yaklaşımıyla değerlendirilmesiyle teorik alıkonma değerleri hesaplanmıştır. Ayrıca farklı pH değerlerindeki mobil fazların aktivite katsayıları değerleri hesaba katılarak doğrusal olmayan regresyon programıyla bileşiklerin termodinamik protonasyon sabitleri ((_s^s)〖pK〗_a) belirlenmiştir. Hidrofobik özellikteki bileşiklerin (_s^s)〖pK〗_a değerleri kullanılarak iki farklı yaklaşımla su ortamındaki protonasyon sabiti değerleri hesaplanmıştır. Çalışma sonunda her iki ekstrapolasyon yönteminden elde edilen sonuçların birbiriyle uyumlu olduğu görülmüştür.

Kaynakça

  • Aronson, J.K., 2016. Meyler’s Side Effects of Drugs. Elsevier, 250-340.
  • Avdeef, A., Sun, N., 2011. A New in situ brain perfusion flow correction method for lipophilic drugs based on the pH-dependent crone-renkin equation. Pharmacological Research, 28, 517–530.
  • Barbosa, J., Barrón, D., Jiménez-Lozano, E., Sanz-Nebot, V., 2001. Comparison between capillary electrophoresis, liquid chromatography, potentiometric and spectrophotometric techniques for evaluation of pKa values of zwitterionic drugs in acetonitrile–water mixtures. Analytica Chimica Acta, 437, 309–321.
  • Barbosa, J., Sanz-Nebot, V., Toro, I., 1996. Solvatochromic parameter values and pH in acetonitrile-water mixtures Optimization of mobile phase for the separation of peptides by high-performance liquid chromatography . Journal of Chromatography A, 725, 249-260.
  • Beltran, J.L., Sanli, N., Fonrodona, G., Barrón, D., Ozkan, G., Barbosa, J., 2003. Spectrophotometric, potentiometric and chromatographic pKa values of polyphenolic substances in water and acetonitrile-water media. Analytica Chimica Acta, 484, 253–264.
  • Bermel, R.A., Hashmonay, R., Meng, X., Randhawa, S., von Rosenstiel, P., Sfikas, N., Kantor, D., 2015. Fingolimod first-doseeffectsinpatients with relapsing multiplesclerosis concomitantly receiving selective serotonin-reuptakeinhibitors. Multiple Sclerosis and Related Disorders, 4, 273–280.
  • Daldal, Y.D., Çakır, C., Yılmaz, H., Demiralay, E.Ç., Özkan, S.A., Alsancak, G., 2014. Liquid Chromatographic, Spectrophotometric and Potentiometric pKa Determination of Ranitidine and Famotidine. Current Drug Therapy, 9, 277-284.
  • Daldal, Y.D., Demiralay, E.Ç., 2022. Development of liquid chromatographic and UV-visible spectrophotometric methods for determination of pKa values of folic acid antimetabolites. Journal of Pharmaceutical and Biomedical Analysis, 212, 1-8.
  • Deák, K., Takács-Novák, K., Tihanyi, K., Béla, N., 2006. Physico-Chemical profiling of antidepressive sertraline: solubility, ionisation, lipophilicity. Medicinal Chemistry, 2,1-6.
  • Herrero-Martínez, J., M., Repollés, C., Bosch, E., Rosés, M., Ràfols, C., 2008. Potentiometric determination of aqueous dissociation constants of flavonols sparingly soluble in water. Talanta, 74, 1008–1013.
  • Hoirisch-Clapauch, S., Nardi, A.E., Gris, J., Brenner, B., 2014. Are the antiplatelet and profibrinolytic properties of selective serotonin-reuptake inhibitors relevant to their brain effects?. Thrombosis Research, 134, 11–16.
  • Jacobsen, N.W., Hansen, C.H., Nellemann, C., Styrishave, B., Halling-Sørensen, B., 2015. Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicology in Vitro, 29, 1729–1735.
  • Kazakevich, Y., Lobrutto, Y., 2007. HPLC for Pharmaceutical Scientists. Wiley-Interscience, 139-249.
  • Li, J., 2002. P rediction of internal standards in reversed-phase liquid chromatography III. Evaluation of an alternative solvation parameter model to correlate and predict the retention of ionizable compounds. Journal of Chromatography A, 982, 209–223.
  • Luan, F., Ma, W., Zhang, H., Zhang, X., Liu, M., Hu, Z., Fan, B., 2005. Prediction of pKa for Neutral and Basic Drugs Based on Radial Basis Function Neural Networks and the Heuristic Method. Pharmaceutical Research, 22(9), 1454-1460.
  • Lunn, G., 2005. HPLC Methods For Recently Approved Pharmaceuticals. John Wiley and Sons, 38-387.
  • Meyer, V.R., 2010. Practical High-Performance Liquid Chromatography. John Wiley and Sons, 5-55.
  • Miguel, L., Barbas, C., 2003. LC determination of impurities in azithromycin tablets. Journal of Pharmaceutical and Biomedical Analysis, 33(2), 211–217.
  • Nane, I.D., Demiralay, E.C., 2021. Thermodynamic protonation constant values of meclizine and buclizine in acetonitrile-water binary mixtures, Journal of Research in Pharmacy, 25(1) , 42–51.
  • Nikitas, P., Pappa-Louisi, A., Agrafiotou, P., 2002. Effect of the organic modifier concentration on the retention in reversed-phase liquid chromatography II. Tests using various simplified models. Journal of chromatography A, 946(1–2), (2002) 33–45.
  • Ortak, H.Y., Demiralay, E.C., 2019. Effect of temperature on the retention of Janus kinase 3 inhibitor in different mobile phase compositions using reversed-phase liquid chromatography, Journal of Pharmaceutical and Biomedical Analysis, 164, 706–712.
  • Rondinini, S., Mussini, P.R., Mussini, T., 1987. Reference value standard and primary standard for pH measurements in organic solvents and water–organic solvent mixtures of moderate to high permittivities. Pure and Applied Chemistry, 59, 1549–1560.
  • Sun, N., Avdeef, A., 2011. Biorelevant pKa (37°C) predicted from the 2D structure of the molecule and its pKa at 25°C. Journal of Pharmaceutical and Biomedical Analysis, 56(2), 173–182.
  • Völgyi, G., Ruiz, R., Box, K., Comer, J., Bosch, E., Takács-Novák, K., 2007. Potentiometric and spectrophotometric pKa determination of water-insoluble compounds: Validation study in a new cosolvent system. Analytica Chimica Acta, 583, 418–428.
  • Volná, T., Motyka, K., Hlaváč, J., 2017. RP-HPLC determination of dissociation constant using solely aqueous mobile phase. Journal of Pharmaceutical and Biomedical Analysis,134, 143–148.
  • Yıldız, A., Genç, Ö., Bektaş, S., 1997. Enstrümental Analiz Yöntemleri. Hacettepe Üniversitesi Yayınları, 321-322.
  • İnternet Kaynakları 1- http://www.chemicalize.org, (01.06.2022)
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Analitik Kimya
Bölüm Makaleler
Yazarlar

Yaşar Doğan Daldal 0000-0003-1211-2686

Ebru Çubuk Demiralay 0000-0002-6270-7509

Yayımlanma Tarihi 27 Ekim 2022
Gönderilme Tarihi 4 Haziran 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 22 Sayı: 5

Kaynak Göster

APA Daldal, Y. D., & Çubuk Demiralay, E. (2022). Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 22(5), 979-988. https://doi.org/10.35414/akufemubid.1126047
AMA Daldal YD, Çubuk Demiralay E. Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. Ekim 2022;22(5):979-988. doi:10.35414/akufemubid.1126047
Chicago Daldal, Yaşar Doğan, ve Ebru Çubuk Demiralay. “Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 22, sy. 5 (Ekim 2022): 979-88. https://doi.org/10.35414/akufemubid.1126047.
EndNote Daldal YD, Çubuk Demiralay E (01 Ekim 2022) Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 22 5 979–988.
IEEE Y. D. Daldal ve E. Çubuk Demiralay, “Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 22, sy. 5, ss. 979–988, 2022, doi: 10.35414/akufemubid.1126047.
ISNAD Daldal, Yaşar Doğan - Çubuk Demiralay, Ebru. “Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 22/5 (Ekim 2022), 979-988. https://doi.org/10.35414/akufemubid.1126047.
JAMA Daldal YD, Çubuk Demiralay E. Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2022;22:979–988.
MLA Daldal, Yaşar Doğan ve Ebru Çubuk Demiralay. “Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 22, sy. 5, 2022, ss. 979-88, doi:10.35414/akufemubid.1126047.
Vancouver Daldal YD, Çubuk Demiralay E. Bazı Selektif Serotonin Geri Alım İnhibitörlerinin Termodinamik Protonasyon Sabitlerinin Su-Asetonitril İkili Karışımlarında Belirlenmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2022;22(5):979-88.