Fenazopiridin Hidroklorür’ün İyonlaşma Sabitinin Analizi: Potansiyometrik Titrasyonda Üç Farklı Ekstrapolasyon Tekniğinin Kullanılması
Year 2014,
Issue: 2, 147 - 157, 01.06.2014
Engin Koçak
Mustafa Çelebier
Sacide Altınöz
Abstract
Bu çalışmanın amacı potantisyometrik titrayondan elde edilen sonuçların değişik ekstrapolasyon yöntemleri ile değerlendirilerek iyonlaşma sabitlerinin bulunması ve bu ekstrapolsayon metodlarının karşılaştırılmasıdır. Suda az miktarda çözünebilen Fenazopiridin hidroklorür model molekül olarak seçilmiş ve çalışmalarda MDM metanol, asetonitril ve 1,4-dioksan – Su karışımları kullanılarak kosolvent iyonlaşma sabitleri hesaplanmıştır. Değişik oranlardaki MDM-Su karışımlarına 0.15M KCl eklenerek eşit iyonik kuvvet sağlanmıştır. Çalışmalarda 0.01M Sodyum hidroksit çözeltisi titrant olarak kullanılmış ve kosolvent iyonlaşma sabitleri belirlenmiştir. Sulu fazdaki iyonlaşma sabiti elde edilen deneysel veriler üç farklı ekstrapolasyon yöntemi ile hasplanmış ve karşılaştırılmıştır. Karşılaştırılan sonuçlar birbirinden çok farklı olamamakla birlikte litaratürde verilen sonuçlarla uyum içerisindendir.
References
- Shang E., Xiang B., Liu G., Xie S., Wei., Lu J.: Determination of pzp in human plasma via LC-MS and subsequent development of a pharmacokinetic model. Analytical and bioanalytical chemistry, 382(1), 216 (2005)
- Farin D., Piva G., Kitzes-Cohen R.: Determination of pzp in human plasma by high performance liquid chromatography. Chromatographia, 52(3-4), 179 (2000)
- Thomas BH., Whitehouse LW., Solomonraj G., Paul CJ.: Excretion of Pzp and Its Metabolites in the Urine of Humans, Rats, Mice, and Guinea-Pigs. J Pharm Sci, 79(4), 321 (1990)
- Poole SK., Patel S., Dehring K, Workman H., Poole CF.: Determination of acid dissociation constants by capillary electrophoresis. Journal of chromatography A, 1037(1-2), 445 (2004)
- Avdeef A., Testa B.: Physicochemical profiling in drug research: a brief survey of the state- of-the-art of experimental techniques. Cellular and molecular life sciences : CMLS, 59(10), 1681 (2000)
- Erdemgil FZ., Sanli S., Sanli N., Ozkan G., Barbosa J., Guiteras J., et al.: Determination of pK(a) values of some hydroxylated benzoic acids in methanol-water binary mixtures by LC methodology and potentiometry. Talanta, 72(2), 489 (2007)
- Evagelou V., Tsantili-Kakoulidou A., Koupparis M.: Determination of the dissociation constants of the cephalosporins cefepime and cefpirome using UV spectrometry and pH potentiometry. Journal of pharmaceutical and biomedical analysis, 31(6), 1119 (2003)
- Andrasi M., Buglyo P., Zekany L., Gaspar A.: A comparative study of capillary zone electrophoresis and pH-potentiometry for determination of dissociation constants. Journal of pharmaceutical and biomedical analysis, 44(5),1040 (2007)
- Anilanmert B., Ozdemir FA., Erdinc N., Pekin M.: Potentiometric determination of the dissociation constants of epirubicin HCl and irinotecan HCl. Mendeleev Commun.,16(2), 97 (2006).
- Rosenberg LS., Simons J., Schulman SG.: Determination of Pka Values of N-Heterocyclic Bases by Fluorescence Spectrophotometry. Talanta., 26(9), 867 (1979)
- Pereira AV., Garabeli AA., Schunemann GD., Borck PC.: Determination of Dissociation Constant (K-a) of Captopril and Nimesulide - Analytical Chemistry Experiments for Undergraduate Pharmacy. Quim Nova., 34(9), 1656 (2011)
- Uhrova M., Miksik I., Deyl Z., Bellini S.: Determination of dissociation constants by separation methods (HPLC and CE). Theoretical background and guidelines for application. Process Contr Qual.,10(1-2), 151 (1997)
- Oumada FZ., Rafols C., Roses M., Bosch E.: Chromatographic determination of aqueous dissociation constants of some water-insoluble nonsteroidal antiinflammatory drugs. J Pharm Sci., 91(4), 991 (2002)
- Babic S., Horvat AJM., Pavlovic DM., Kastelan-Macan M.: Determination of pK(a) values of active pharmaceutical ingredients. Trac-Trend Anal Chem., 26(11), 1043 (2007)
- Gribbon P., Sewing A.: High-throughput drug discovery: what can we expect from HTS? Drug discovery today, 10(1), 17 (2005)
- Box KJ., Volgyi G., Baka E., Stuart M., Takacs-Novak K., Comer JE.: Equilibrium versus kinetic measurements of aqueous solubility, and the ability of compounds to supersaturate in solution--a validation study. J Pharm Sci., 95(6), 1298 (2006)
- Volgyi G., Ruiz R., Box K., Comer J., Bosch E., Takacs-Novak K.: Potentiometric and spectrophotometric pKa determination of water-insoluble compounds: validation study in a new cosolvent system. Analytica chimica acta, 583(2), 418 (2007)
- Deligny CL.: The Dissociation Constants of Some Aliphatic Amines in Water and Methanol- Water Mixtures at 25-Degrees. Recl Trav Chim Pay B., 79(6), 731 (1960)
- Grunwald E., Berkowitz BJ.: The Measurement and Correlation of Acid Dissociation Constants for Carboxylic Acids in the System Ethanol Water - Activity Coefficients and Empirical Activity Functions. J Am Chem Soc., 73(10), 4939 (1951)
- Papadopoulos N., Avranas A.: Dissociation of Salicylic-Acid, 2,4-Dihydroxybenzoic Acids, 2,5-Dihydroxybenzoic Acids and 2,6-Dihydroxybenzoic Acids in 1-Propanol - Water Mixtures at 25-Degrees-C. J Solution Chem., 20(3), 293 (1991)
- Siow KS., Ang KP.: Thermodynamics of Ionization of 2,4,-Dinitrophenol in Water- Dimethylsulfoxide Solvents. J Solution Chem., 18(10), 937 (1989)
- Cavill GWK., Gibson NA., Nyholm RS.: The Dissociation Constants of Some Para- Alkoxybenzoic Acids. J Chem Soc., 2466 (1949)
- Garrett ER.: Basis of hydrogen ion binding curves deduced from differences in solution and solvent titrations. J Pharm Sci., 963, 52, 400 (1963)
- Avdeef A., Box KJ., Comer JEA., Gilges M., Hadley M., Hibbert C., et al.: PH-metric log P 11. pK(a) determination of water-insoluble drugs in organic solvent-water mixtures. Journal of pharmaceutical and biomedical analysis., 20(4), 631 (1999)
- Avdeef A., Comer JEA., Thomson SJ.: Ph-Metric Log .3. Glass-Electrode Calibration in Methanol Water, Applied to Pka Determination of Water-Insoluble Substances. Anal Chem., 65(1), 42 (1993)
- Bergstrom CAS., Strafford M, Lazorova L., Avdeef A., Luthman K., Artursson P.: Absorption classification of oral drugs based on molecular surface properties. J Med Chem., 46(4), 558 (2003)
- Yasuda M.: Dissociation Constants of Some Carboxylic Acids in Mixed Aqueous Solvents. B Chem Soc Jpn., 32(5), 429 (1959)
- Takacs Novak K., Box KJ., Avdeef A.: Potentiometric pK(a) determination of water-insoluble compounds: Validation study in methanol/water mixtures. Int J Pharm., 151(2), 235 (1997)
- Box, K., Comer, J., Grovestock, T. Mole, J.: A method for assessing dissolution, supersaturation and precipitation of a drug during passage through the gastro-intestinal tract. Sirus Analytical LTD.
Dissociation Constant Determination of Phenazopyridine Hydrocholoride: Using Three Different Extrapolation Techniques on Potentiometric Titration
Year 2014,
Issue: 2, 147 - 157, 01.06.2014
Engin Koçak
Mustafa Çelebier
Sacide Altınöz
Abstract
There are lots of publications reported about the biological activities of various synthesized compounds but it is rarely discussed the physicochemical properties of these substances as an additional/supporting data on biological activity. Acid dissociation constant is highly related with the ability or inability of the compounds to cross the cell membranes, and therefore it is a great importance to know the pKa of any potential active compound in order to classify and understand the behavior related with the permeability in the system of the body. Potentiometric titration is a well-known and easy to apply technique for determination of the dissociation constant of any ionized compound. The disadvantage of potentiometric titrations is that the concentration of the pharmaceutical solution must be high enough to indicate the equation point on analysis. It is not always possible to work with high concentrations if the compounds are slightly soluble in aqueous solutions. The application of MDM–water mixtures improves the solubility of poorly water soluble compounds, thus, their psKa values can be calculated easily in lower percentage of organic solvents. The aqueous pKa values could be easily obtained by using extrapolation techniques. The MDM–water mixtures do not cause large shifts on psKa values. In this study, the application of three different extrapolation techniques was shown by using pzp HCl as a model molecule and it was concluded that extrapolation results were very close to the reported pKa value of pzp HCl. Thus, it was shown that the extrapolation techniques could be easily applied for determination of the pKa values of any drug candidate molecule.
References
- Shang E., Xiang B., Liu G., Xie S., Wei., Lu J.: Determination of pzp in human plasma via LC-MS and subsequent development of a pharmacokinetic model. Analytical and bioanalytical chemistry, 382(1), 216 (2005)
- Farin D., Piva G., Kitzes-Cohen R.: Determination of pzp in human plasma by high performance liquid chromatography. Chromatographia, 52(3-4), 179 (2000)
- Thomas BH., Whitehouse LW., Solomonraj G., Paul CJ.: Excretion of Pzp and Its Metabolites in the Urine of Humans, Rats, Mice, and Guinea-Pigs. J Pharm Sci, 79(4), 321 (1990)
- Poole SK., Patel S., Dehring K, Workman H., Poole CF.: Determination of acid dissociation constants by capillary electrophoresis. Journal of chromatography A, 1037(1-2), 445 (2004)
- Avdeef A., Testa B.: Physicochemical profiling in drug research: a brief survey of the state- of-the-art of experimental techniques. Cellular and molecular life sciences : CMLS, 59(10), 1681 (2000)
- Erdemgil FZ., Sanli S., Sanli N., Ozkan G., Barbosa J., Guiteras J., et al.: Determination of pK(a) values of some hydroxylated benzoic acids in methanol-water binary mixtures by LC methodology and potentiometry. Talanta, 72(2), 489 (2007)
- Evagelou V., Tsantili-Kakoulidou A., Koupparis M.: Determination of the dissociation constants of the cephalosporins cefepime and cefpirome using UV spectrometry and pH potentiometry. Journal of pharmaceutical and biomedical analysis, 31(6), 1119 (2003)
- Andrasi M., Buglyo P., Zekany L., Gaspar A.: A comparative study of capillary zone electrophoresis and pH-potentiometry for determination of dissociation constants. Journal of pharmaceutical and biomedical analysis, 44(5),1040 (2007)
- Anilanmert B., Ozdemir FA., Erdinc N., Pekin M.: Potentiometric determination of the dissociation constants of epirubicin HCl and irinotecan HCl. Mendeleev Commun.,16(2), 97 (2006).
- Rosenberg LS., Simons J., Schulman SG.: Determination of Pka Values of N-Heterocyclic Bases by Fluorescence Spectrophotometry. Talanta., 26(9), 867 (1979)
- Pereira AV., Garabeli AA., Schunemann GD., Borck PC.: Determination of Dissociation Constant (K-a) of Captopril and Nimesulide - Analytical Chemistry Experiments for Undergraduate Pharmacy. Quim Nova., 34(9), 1656 (2011)
- Uhrova M., Miksik I., Deyl Z., Bellini S.: Determination of dissociation constants by separation methods (HPLC and CE). Theoretical background and guidelines for application. Process Contr Qual.,10(1-2), 151 (1997)
- Oumada FZ., Rafols C., Roses M., Bosch E.: Chromatographic determination of aqueous dissociation constants of some water-insoluble nonsteroidal antiinflammatory drugs. J Pharm Sci., 91(4), 991 (2002)
- Babic S., Horvat AJM., Pavlovic DM., Kastelan-Macan M.: Determination of pK(a) values of active pharmaceutical ingredients. Trac-Trend Anal Chem., 26(11), 1043 (2007)
- Gribbon P., Sewing A.: High-throughput drug discovery: what can we expect from HTS? Drug discovery today, 10(1), 17 (2005)
- Box KJ., Volgyi G., Baka E., Stuart M., Takacs-Novak K., Comer JE.: Equilibrium versus kinetic measurements of aqueous solubility, and the ability of compounds to supersaturate in solution--a validation study. J Pharm Sci., 95(6), 1298 (2006)
- Volgyi G., Ruiz R., Box K., Comer J., Bosch E., Takacs-Novak K.: Potentiometric and spectrophotometric pKa determination of water-insoluble compounds: validation study in a new cosolvent system. Analytica chimica acta, 583(2), 418 (2007)
- Deligny CL.: The Dissociation Constants of Some Aliphatic Amines in Water and Methanol- Water Mixtures at 25-Degrees. Recl Trav Chim Pay B., 79(6), 731 (1960)
- Grunwald E., Berkowitz BJ.: The Measurement and Correlation of Acid Dissociation Constants for Carboxylic Acids in the System Ethanol Water - Activity Coefficients and Empirical Activity Functions. J Am Chem Soc., 73(10), 4939 (1951)
- Papadopoulos N., Avranas A.: Dissociation of Salicylic-Acid, 2,4-Dihydroxybenzoic Acids, 2,5-Dihydroxybenzoic Acids and 2,6-Dihydroxybenzoic Acids in 1-Propanol - Water Mixtures at 25-Degrees-C. J Solution Chem., 20(3), 293 (1991)
- Siow KS., Ang KP.: Thermodynamics of Ionization of 2,4,-Dinitrophenol in Water- Dimethylsulfoxide Solvents. J Solution Chem., 18(10), 937 (1989)
- Cavill GWK., Gibson NA., Nyholm RS.: The Dissociation Constants of Some Para- Alkoxybenzoic Acids. J Chem Soc., 2466 (1949)
- Garrett ER.: Basis of hydrogen ion binding curves deduced from differences in solution and solvent titrations. J Pharm Sci., 963, 52, 400 (1963)
- Avdeef A., Box KJ., Comer JEA., Gilges M., Hadley M., Hibbert C., et al.: PH-metric log P 11. pK(a) determination of water-insoluble drugs in organic solvent-water mixtures. Journal of pharmaceutical and biomedical analysis., 20(4), 631 (1999)
- Avdeef A., Comer JEA., Thomson SJ.: Ph-Metric Log .3. Glass-Electrode Calibration in Methanol Water, Applied to Pka Determination of Water-Insoluble Substances. Anal Chem., 65(1), 42 (1993)
- Bergstrom CAS., Strafford M, Lazorova L., Avdeef A., Luthman K., Artursson P.: Absorption classification of oral drugs based on molecular surface properties. J Med Chem., 46(4), 558 (2003)
- Yasuda M.: Dissociation Constants of Some Carboxylic Acids in Mixed Aqueous Solvents. B Chem Soc Jpn., 32(5), 429 (1959)
- Takacs Novak K., Box KJ., Avdeef A.: Potentiometric pK(a) determination of water-insoluble compounds: Validation study in methanol/water mixtures. Int J Pharm., 151(2), 235 (1997)
- Box, K., Comer, J., Grovestock, T. Mole, J.: A method for assessing dissolution, supersaturation and precipitation of a drug during passage through the gastro-intestinal tract. Sirus Analytical LTD.