Research Article
Year 2018,
Volume: 22 Issue: 4, 528 - 535, 27.06.2025
Abstract
References
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- [2] Ritschel WA, Kearns GL. Handbook of Basic Pharmacokinetics - Including Clinical Applications. Washington, DC: American Pharmacists Association, USA; 2004.
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- [4] Alanne AL, Hyvonen H, Lahtinen M, Ylisirnio M, Turhanen P, Kolehmainen E, Peraniemi S, Vepsalainen J. Systematic Study of the Physicochemical Properties of a Homologous Series of Aminobisphosphonates. Molecules. 2012; 17(9):10928-10945.
- [5] Box KJ, Volgyi G, Ruiz R, Comer JE, Takacs-Novak K, Bosch E, Rafols C, Roses M. Physicochemical Properties of a New Multicomponent Cosolvent System for the pKa Determination of Poorly Soluble Pharmaceutical Compounds. Helv Chim Acta. 2007; 90(8):1538-1553.
- [6] Fu XC, Liang WQ, Ma WX. Relationships Between the Release of Soluble Drugs from HPMC Matrices and the Physicochemical Properties of Drugs. Pharmazie. 2003; 58(3):221-222.
- [7] Schmitt-Willich H, Brehm M, Ewers CLJ, Michl G, Muller-Fahrnow A, Petrov O, Platzek J, Raduchel B, Sulzle D. Synthesis and Physicochemical Characterization of a New Gadolinium Chelate: The liver-specific Magnetic Resonance Imaging Contrast Agent Gd-EOB-DTPA. Inorg Chem. 1999; 38(6):1134-1144.
- [8] Ho NF, Sims SM, Vidmar TJ, Day JS, Barsuhn CL, Thomas EM, Geary TG, Thompson DP. Theoretical Perspectives on Anthelmintic Drug Discovery: Interplay of Transport Kinetics, Physicochemical Properties, and in vitro Activity of Anthelmintic Drugs. J Pharm Sci. 1994; 83(7):1052-1059.
- [9] Lee PH, Ayyarnpalayarn SN, Carreira LA, Shalaeva M, Bhattachar S, Coselmon R, Poole S, Gifford E, Lombardo F. In silico Prediction of Ionization Constants of Drugs. Mol Pharm. 2007; 4(4):498-512.
- [10] Ekins S, Mestres J, Testa B. In silico Pharmacology for Drug discovery: Applications to Targets and Beyond. Brit J Pharmacol. 2007; 152(1):21-37.
- [11] Ramsay AG. Clinical Application of the Henderson-Hasselbalch Equation. Appl Ther. 1965; 7(9):730-736.
- [12] Merck Manual. Overview of Pharmacokinetics. http://www.merckmanuals.com (accessed Sep 8, 2015).
- [13] Food and Drug Administration, FDA. Available from: http://www.fda.gov (accessed Sep 8, 2015).
- [14] Van de Waterbeemd H. The Fundamental Variables of the Biopharmaceutics Classification System (BCS): A Commentary. Eur J Pharm Sci. 1998; 7(1):1-3.
- [15] Demiralay EC, Alsancak G, Ozkan SA. Determination of pKa Values of Nonsteroidal Anti-Inflammatory Drug Oxicams by RP-HPLC and Their Analysis in Pharmaceutical Dosage Forms. J Sep Sci. 2009; 32:2928-2936.
- [16] Wiczling P, Kawczak P, Nasal A, Kaliszan R. Simultaneous Determination of pKa and Lipophilicity by Gradient RP HPLC. Anal Chem. 2006; 78(1):239-249.
- [17] Celik H, Buyukaga M, Celebier M, Turkoz Acar E, Baymak MS, Gokhan-Kelekci N, Palaska E, Erdogan H. Determination of pKa Values of Some Benzoxazoline Derivatives and the Structure-Activity Relationship. J Chem Eng Data. 2013; 58(6):1589-1596.
- [18] Dohoda D, Tsinman K, Tsinman O, Wang H, Tam KY. Spectrophotometric pKa Determination of Ionizable Pharmaceuticals: Resolution of Molecules with Weak pH-Dependent Spectral Shift. J Pharm Biomed Anal. 2015; 114:88-96.
- [19] Miyaji Y, Fujii Y, Takeyama S, Kawai Y, Kataoka M, Takahashi M, Yamashita S. Advantage of the Dissolution/Permeation System for Estimating Oral Absorption of Drug Candidates in the Drug Discovery Stage. Mol Pharm. 2016; 13(5):1564-1574.
- [20] Sun N, Avdeef A. Biorelevant pKa (37 °C) Predicted from the 2D Structure of the Molecule and its pKa at 25 °C. J Pharm Biomed Anal. 2011; 56(2):173-182.
- [21] Ahuja S, Dong MW. Handbook of Pharmaceutical Analysis by HPLC. Waltham: Elsevier, Academic Press, USA; 2005.
- [22] Albert A, Serjeant EP. Ionization Constants of Acids and Bases: a Laboratory Manual. Methuen London: Wiley, USA; 1962.
- [23] OECD Guideline for the Testing of Chemicals. Partition Coefficient (n-octanol/water): Shake Flask Method, 107, 27.07.95. http://www.oecd-ilibrary.org (accessed Sep 8, 2015).
Investigating the physicochemical properties of phenazopyridine hydrochloride using high-performance liquid chromatography and UV-visible spectrophotometry
Abstract
The purpose of this study is to develop high-performance liquid chromatography (HPLC) and ultravioletvisible (UV-Vis) spectrophotometry methods for the determination of pKa, log P, and log D values of phenazopyridine hydrochloride (PHCl). For the HPLC analysis, the pH of the mobile phase was plotted against the capacity factor, and the pKa value was obtained from a sigmoidal relationship. Meanwhile, for the UV-Vis spectrophotometric study, the absorbance of PHCl was plotted against pH at 332 nm to obtain the pKa value. The log P and log D (at pH 2.0) values were then calculated based on the concentration of PHCl in the octanol/water phase. Using the HPLC method, the pKa value was established as 5.05 (± 0.15). Meanwhile, the spectroscopic technique afforded pKa values of 5.20 (± 0.22) and 5.17 (± 0.17) via a classical sigmoidal curve and the Albert and Serjeant method. The log D (at pH 2.0) and log P values of PHCl were 1.61 (± 0.16) and 2.62 (± 0.11), respectively. The obtained results are in good agreement with each other. The pKa, log P, and log D values of PHCl can be determined by HPLC and UV-Vis spectrophotometry with reproducible results.
References
- [1] Smith DA, Allerton C, Kalgutkar AS, Waterbeemd H, Walker DK. Pharmacokinetics and Metabolism in Drug Design. Weinheim: Wiley-VCH, USA; 2012.
- [2] Ritschel WA, Kearns GL. Handbook of Basic Pharmacokinetics - Including Clinical Applications. Washington, DC: American Pharmacists Association, USA; 2004.
- [3] Avdeef A, Testa B. Physicochemical Profiling in Drug Research: A Brief Survey of the State-of-the-Art of Experimental Techniques. Cell Mol Life Sci. 2002; 59(10):1681-1689.
- [4] Alanne AL, Hyvonen H, Lahtinen M, Ylisirnio M, Turhanen P, Kolehmainen E, Peraniemi S, Vepsalainen J. Systematic Study of the Physicochemical Properties of a Homologous Series of Aminobisphosphonates. Molecules. 2012; 17(9):10928-10945.
- [5] Box KJ, Volgyi G, Ruiz R, Comer JE, Takacs-Novak K, Bosch E, Rafols C, Roses M. Physicochemical Properties of a New Multicomponent Cosolvent System for the pKa Determination of Poorly Soluble Pharmaceutical Compounds. Helv Chim Acta. 2007; 90(8):1538-1553.
- [6] Fu XC, Liang WQ, Ma WX. Relationships Between the Release of Soluble Drugs from HPMC Matrices and the Physicochemical Properties of Drugs. Pharmazie. 2003; 58(3):221-222.
- [7] Schmitt-Willich H, Brehm M, Ewers CLJ, Michl G, Muller-Fahrnow A, Petrov O, Platzek J, Raduchel B, Sulzle D. Synthesis and Physicochemical Characterization of a New Gadolinium Chelate: The liver-specific Magnetic Resonance Imaging Contrast Agent Gd-EOB-DTPA. Inorg Chem. 1999; 38(6):1134-1144.
- [8] Ho NF, Sims SM, Vidmar TJ, Day JS, Barsuhn CL, Thomas EM, Geary TG, Thompson DP. Theoretical Perspectives on Anthelmintic Drug Discovery: Interplay of Transport Kinetics, Physicochemical Properties, and in vitro Activity of Anthelmintic Drugs. J Pharm Sci. 1994; 83(7):1052-1059.
- [9] Lee PH, Ayyarnpalayarn SN, Carreira LA, Shalaeva M, Bhattachar S, Coselmon R, Poole S, Gifford E, Lombardo F. In silico Prediction of Ionization Constants of Drugs. Mol Pharm. 2007; 4(4):498-512.
- [10] Ekins S, Mestres J, Testa B. In silico Pharmacology for Drug discovery: Applications to Targets and Beyond. Brit J Pharmacol. 2007; 152(1):21-37.
- [11] Ramsay AG. Clinical Application of the Henderson-Hasselbalch Equation. Appl Ther. 1965; 7(9):730-736.
- [12] Merck Manual. Overview of Pharmacokinetics. http://www.merckmanuals.com (accessed Sep 8, 2015).
- [13] Food and Drug Administration, FDA. Available from: http://www.fda.gov (accessed Sep 8, 2015).
- [14] Van de Waterbeemd H. The Fundamental Variables of the Biopharmaceutics Classification System (BCS): A Commentary. Eur J Pharm Sci. 1998; 7(1):1-3.
- [15] Demiralay EC, Alsancak G, Ozkan SA. Determination of pKa Values of Nonsteroidal Anti-Inflammatory Drug Oxicams by RP-HPLC and Their Analysis in Pharmaceutical Dosage Forms. J Sep Sci. 2009; 32:2928-2936.
- [16] Wiczling P, Kawczak P, Nasal A, Kaliszan R. Simultaneous Determination of pKa and Lipophilicity by Gradient RP HPLC. Anal Chem. 2006; 78(1):239-249.
- [17] Celik H, Buyukaga M, Celebier M, Turkoz Acar E, Baymak MS, Gokhan-Kelekci N, Palaska E, Erdogan H. Determination of pKa Values of Some Benzoxazoline Derivatives and the Structure-Activity Relationship. J Chem Eng Data. 2013; 58(6):1589-1596.
- [18] Dohoda D, Tsinman K, Tsinman O, Wang H, Tam KY. Spectrophotometric pKa Determination of Ionizable Pharmaceuticals: Resolution of Molecules with Weak pH-Dependent Spectral Shift. J Pharm Biomed Anal. 2015; 114:88-96.
- [19] Miyaji Y, Fujii Y, Takeyama S, Kawai Y, Kataoka M, Takahashi M, Yamashita S. Advantage of the Dissolution/Permeation System for Estimating Oral Absorption of Drug Candidates in the Drug Discovery Stage. Mol Pharm. 2016; 13(5):1564-1574.
- [20] Sun N, Avdeef A. Biorelevant pKa (37 °C) Predicted from the 2D Structure of the Molecule and its pKa at 25 °C. J Pharm Biomed Anal. 2011; 56(2):173-182.
- [21] Ahuja S, Dong MW. Handbook of Pharmaceutical Analysis by HPLC. Waltham: Elsevier, Academic Press, USA; 2005.
- [22] Albert A, Serjeant EP. Ionization Constants of Acids and Bases: a Laboratory Manual. Methuen London: Wiley, USA; 1962.
- [23] OECD Guideline for the Testing of Chemicals. Partition Coefficient (n-octanol/water): Shake Flask Method, 107, 27.07.95. http://www.oecd-ilibrary.org (accessed Sep 8, 2015).
There are 23 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmaceutical Analytical Chemistry |
| Journal Section | Articles |
| Authors | |
| Publication Date | June 27, 2025 |
| Published in Issue | Year 2018 Volume: 22 Issue: 4 |