Asetonitril-Su İkili Karışımlarında Piroksikam ve Tenoksikam'ın Potansiyometrik pKa Tayini

Year 2012, Volume: 7 Issue: 1, 34 - 44, 04.06.2012

Ebru Çubuk Demiralay , Hülya Yılmaz

Abstract

İyonlaşma sabiti (pKa) çözünebilirlik sınırlaması olmaksızın doğru tahmin edilebilen parametrelerden birisidir. Sunulan bu çalışmada, piroksikam ve tenoksikamın asit- baz davranışı çalışılmıştır. Potansiyometrik metot kullanılarak, piroksikam ve tenoksikamın pKa değerleri asetonitril-su ikili karışımlarının farklı yüzdelerinde tayin edilmiştir (asetonitril içeriği hacimce % 30 ile 45 arasında). Bu bileşiklerin sudaki pKa değerleri mol kesri ve Yasuda-Shedlovsky eşitlikleri kullanarak hesaplanmıştır. Deneysel pKa değerleri SPARC and Marvin Sketch paket programlarından türetilmiş tahmini değerlerle karşılaştırılmıştır.

Keywords

Potansiyometrik titrasyonlar, Asetonitril, pKa, Yasuda- Shedlovsky eşitliği

Potentiometric pKa Determination of Piroxicam and Tenoxicam in Acetonitrile-Water Binary Mixtures

Abstract

Ionization constant (pKa) is one among the parameter to be estimated with accuracy, irrespective of solubility constraints. In the present study, acid-base behaviour of the piroxicam and tenoxicam was studied. By using the potentiometric method, pKa values of piroxicam and tenoxicam have been determined in different percentage of acetonitrile-water binary mixtures (acetonitrile content between 30 and 45% in volume). Aqueous pKa values of these compounds were calculated by mole fraction and Yasuda - Shedlovsky equations. The experimental pKa values were compared to the corresponding predicted values derived by SPARC and Marvin Sketch software packages.

Keywords

Potentiometric titrations, Acetonitrile, pKa, Yasuda- Shedlovsky Equation

References

• Lombardino J.G., Wiseman E.H., 1982. The oxicams: A new class of nonsteroidal antiinflammatory agents, Trends Pharmacology Science, 2: 132-135.
• Vatrtiainen N., Huang C.Y., Salminen A., Goldsteins G., Chan P.H., Koistinaho J., 2001. Piroxicam and NS-398 rescue neurones from hypoxia/reoxygenation damage by a mechanism independent of cyclo-oxygenase inhibition, Journal of Neurochemistry, 76: 480-489.
• Goodman&Gilman A., The pharmacological basis of therapeutics, Ninth Ed., The McGraw-Hill Comp., 1996.
• Starek M., Krzek J., 2008. A review of analytical techniques for determination of oxicams, nimesulide and nabumetone, Talanta, 77: 925-942.
• Garrido G., Nogales V., Ráfols C., Bosch E., 2007. Acidity of several polyprotic acids, amiodarone and quetiapine hemifumarate in pure methanol, Talanta,73: 115-120.
• Sanli S., Sanli N., Alsancak G., 2009. Determination of Protonation Constants of Some Tetracycline Antibiotics by Potentiometry and LC Methods in Water and Acetonitrile- Water Binary Mixtures, Journal of Brazillian Chemical Society, 20: 939-946.
• Sanli N., Sanli S., Alsancak G., 2010. Determination of Dissociation Constants of Folinic Acid (Leucovorin), 5-Fluorouracil, and Irinotecan in Hydro-organic Media by a Spectrophotometric Method, Journal of Chemical Enginering Data, 55: 2695-2699.
• Demiralay E.C., Alsancak G., Ozkan S.A., 2009. Determination of pKa values of nonsteroidal antiinflammatory drug-oxicams by RP–HPLC and their analysis in pharmaceutical dosage forms, Journal of Separation Science, 32(17): 2928-2936.
• Demiralay E.C., Cubuk B., Alsancak G., Ozkan S.A., 2010. Combined Effect of Polarity and pH On The Chromatographic Behaviour of Some Angiotensin II Receptor Antagonists and Optimization of Their Determination in Pharmaceutical Dosage Forms, Pharmaceutical and Biomedical Analysis, 53: 475-482. Journal of
• Ishihama Y. M., Nakamura T., Miwa T. Kajima N., Asakawa A., 2002. Rapid method for pKa determination of drugs using pressure-assisted capillary electrophoresis with photodiode array detection in drug discovery, Journal of Pharmacy Science, 91: 933-942. SPARC http://ibmlc2.chem.uga.edu/sparc/index.cfm,2011 line Calculator, University of Georgia, USA,
• Hilal S.H. Carreira L.A. and Karickhoff S.W. Verification and Validation of the SPARC model, EPA/600/R-03/033 (March 2003).
• Marvin Sketch program, Chemaxon, http://www.chemaxon.com, 2011
• Yasuda M., 1959. Dissociation constants of some carboxylic acids in mixed aqueous solvents, Bulletin of the Chemical Society of Japan, 32: 429-432.
• Shedlovsky T., 1962. In: Peasce B, editor. Electrolytes. Pergamon Press, New York, p.146-151.
• Takács- Novák K., Kökösi J., Podányi B., Noszál B., Tsai R.S., Lisa G, Carrupt P.A., Testa B., 2004. Microscopic Protonation/Deprotonation Equilibria of the Anti-Inflammatory Agent Piroxicam, Helvetica Chimica Acta, 78(3): 553-562.
• Koczián K., Kökösi J., Mazák K., Noszál B., 2005. Novel Chemical Transformations of Tenoxicam, Helvetica Chimica Acta, 88: 2355-2363.
• Tsai R.S., Carrupt P.A., Tayar N.E., Giroud Y., Andrade P., Testa B. 1993. Physicochemical and structural properties of non-steroidal anti-inflammatory oxicams, Helvetica Chimica Acta, 76: 842-854.
• Bernhard E., Zimmermann F., 1984. Contribution to the understanding of oxicam ionization constants, Arzneimittel Forschung - Drug Research, 34 : 647-648.
• Ho J., Coote M.L., Franco- Perez M., Gómez-Balderas R., 2010. First-principles prediction of the pK(a)s of anti-inflammatory oxicams, The Journal of Physical Chemistry, 114: 1992-2003.
• David V., Albu F., Medvedovici A., 2005.Structure-Retention Correlation of Some Oxicam Drugs in Reversed-Phase Liquid Chromatography, Technology, 27 (6) : 965-984.
• Journal of Liquid Chromatography & Related
• Gran G., 1952. Determination of the Equivalence Point in Potentiometric Titrations. Part II, Analyst, 7: 661–671.
• Serjeant E.P., 1984. Potentiometry and Potentiometric Titrations, Wiley, New York.
• Miyake K., Okumura K., Terada H., 1985. Determination of Acid Dissociation Constants by reversed phase liquid chromatography, Chemical and Pharmaceutical Bulletin 33(2) : 769-777.
• Barbosa J., Baron D., Beltran J.L., Sanz Nebot V., 1995. PKPOT, a program for the potentiometric study of ionic equilibria in aqueous and non-aqueous media, Analytica Chimica Acta, 317: 75- 81.
• Barbosa J., Bergés R., I. Toro, V. Sanz-Nebot, 1997. Dissociation constants and preferential solvation of fluoroquinolones in hydroorganic mixtures used in LC, International Journal of Pharmaceutics, 149: 213-225.
• Augustin-Nowacka D., Chmurzyñski L., 1999. A potentiometric study of acid–base equilibria of substituted pyridines in acetonitrile, Analytica Chimica Acta, 381: 215-220.
• Chmurzyński L., 1992. Acid-base equilibria of substituted pyridine N-oxides in methanol, Journal of Solution Chemistry, 21: 171-178.
• Hülya Yılmaz e-mail: [e-mail]