Research Article
Elucidating Ionization Behavior: Potentiometric Titration for Precise Determination of pKa Values in Medicinal Chemistry
Abstract
The determination of pKa values holds paramount importance in the field of medicinal chemistry, serving as a critical parameter for understanding the ionization behavior of pharmaceutical compounds. This study employs potentiometric titration as a precise method to elucidate the pKa values of diverse molecules. The experimental methodology involved a carefully controlled titration setup, utilizing a pH meter to monitor the titration curve and identify inflection points corresponding to the dissociation of acidic or basic functional groups.
References
- 1. Babić S, Horvat AJ, Pavlović DM, Kaštelan-Macan M. Determination of pKa values of active pharmaceutical ingredients. TrAC Trends in Analytical Chemistry. 2007;26(11):1043-1061. [CrossRef]
- 2. Reijenga J, Van Hoof A, Van Loon A, Teunissen B. Development of methods for the determination of pKa values. Analytical Chemistry Insights. 2013;8:ACI. S12304. [CrossRef]
- 3. Fallavena PRB, Schapoval EE. pKa determination of nimesulide in methanol—water mixtures by potentiometric titrations. International Journal of Pharmaceutics. 1997;158(1):109-112. [CrossRef]
- 4. Bacarella A, Grunwald E, Marshall H, Purlee EL. The potentiometric measurement of acid dissociation constants and pH in the system methanol-water. pKa values for carboxylic acids and anilinium ions. The Journal of Organic Chemistry. 1955;20(6):747-762. [CrossRef]
- 5. Avdeef A, Comer JE, Thomson SJ. pH-Metric log P. 3. Glass electrode calibration in methanol-water, applied to pKa determination of water-insoluble substances. Analytical Chemistry. 1993;65(1):42-49. [CrossRef]
- 6. Benet LZ, Goyan JE. Potentiometric determination of dissociation constants. Journal of Pharmaceutical Sciences. 1967;56(6):665-680. [CrossRef]
- 7. Ravichandiran V, Devarajan V, Masilamani K. Determination of ionization constant (pKa) for poorly soluble drugs by using surfactants: a novel approach. Der Pharmacia Lettre. 2011;3(4):183-92.
- 8. Völgyi G, Ruiz R, Box K, et al. Potentiometric and spectrophotometric pKa determination of water-insoluble compounds: validation study in a new cosolvent system. Analytica Chimica Acta. 2007;583(2):418-428. [CrossRef]
- 9. Murakami T. Absorption sites of orally administered drugs in the small intestine. Expert Opinion on Drug Discovery. 2017;12(12):1219-1232. [CrossRef]
- 10. Salehi N, Kuminek G, Al-Gousous J, et al. Improving dissolution behavior and oral absorption of drugs with pH-dependent solubility using ph modifiers: a physiologically realistic mass transport analysis. Molecular Pharmaceutics. 2021;18(9):3326-3341. [CrossRef]
- 11. Remko M. Theoretical study of molecular structure, pKa, lipophilicity, solubility, absorption, and polar surface area of some hypoglycemic agents. Journal of Molecular Structure: THEOCHEM. 2009;897(1-3):73-82. [CrossRef]
- 12. Hale T, Abbey J. Drug transfer during breast-feeding. Fetal and Neonatal Physiology. Elsevier; 2017:239-248. e5.
- 13. Acharya PC, Marwein S, Mishra B, et al. Role of salt selection in drug discovery and development. Dosage Form Design Considerations. Elsevier; 2018:435-472. [CrossRef]
- 14. Serajuddin AT. Salt formation to improve drug solubility. Advanced Drug Delivery Reviews. 2007;59(7):603-616. [CrossRef]
- 15. Patel P, Ibrahim NM, Cheng K. The importance of apparent pKa in the development of nanoparticles encapsulating siRNA and mRNA. Trends in Pharmacological Sciences. 2021;42(6):448-460. [CrossRef]
- 16. Caldwell GW, Ritchie DM, Masucci JA, Hageman W, Yan Z. The new pre-preclinical paradigm: compound optimization in early and late phase drug discovery. Current Topics in Medicinal Chemistry. 2001;1(5):353-366. [CrossRef]
Year 2024,
Volume: 4 Issue: 2, 46 - 50, 23.04.2024
Abstract
References
- 1. Babić S, Horvat AJ, Pavlović DM, Kaštelan-Macan M. Determination of pKa values of active pharmaceutical ingredients. TrAC Trends in Analytical Chemistry. 2007;26(11):1043-1061. [CrossRef]
- 2. Reijenga J, Van Hoof A, Van Loon A, Teunissen B. Development of methods for the determination of pKa values. Analytical Chemistry Insights. 2013;8:ACI. S12304. [CrossRef]
- 3. Fallavena PRB, Schapoval EE. pKa determination of nimesulide in methanol—water mixtures by potentiometric titrations. International Journal of Pharmaceutics. 1997;158(1):109-112. [CrossRef]
- 4. Bacarella A, Grunwald E, Marshall H, Purlee EL. The potentiometric measurement of acid dissociation constants and pH in the system methanol-water. pKa values for carboxylic acids and anilinium ions. The Journal of Organic Chemistry. 1955;20(6):747-762. [CrossRef]
- 5. Avdeef A, Comer JE, Thomson SJ. pH-Metric log P. 3. Glass electrode calibration in methanol-water, applied to pKa determination of water-insoluble substances. Analytical Chemistry. 1993;65(1):42-49. [CrossRef]
- 6. Benet LZ, Goyan JE. Potentiometric determination of dissociation constants. Journal of Pharmaceutical Sciences. 1967;56(6):665-680. [CrossRef]
- 7. Ravichandiran V, Devarajan V, Masilamani K. Determination of ionization constant (pKa) for poorly soluble drugs by using surfactants: a novel approach. Der Pharmacia Lettre. 2011;3(4):183-92.
- 8. Völgyi G, Ruiz R, Box K, et al. Potentiometric and spectrophotometric pKa determination of water-insoluble compounds: validation study in a new cosolvent system. Analytica Chimica Acta. 2007;583(2):418-428. [CrossRef]
- 9. Murakami T. Absorption sites of orally administered drugs in the small intestine. Expert Opinion on Drug Discovery. 2017;12(12):1219-1232. [CrossRef]
- 10. Salehi N, Kuminek G, Al-Gousous J, et al. Improving dissolution behavior and oral absorption of drugs with pH-dependent solubility using ph modifiers: a physiologically realistic mass transport analysis. Molecular Pharmaceutics. 2021;18(9):3326-3341. [CrossRef]
- 11. Remko M. Theoretical study of molecular structure, pKa, lipophilicity, solubility, absorption, and polar surface area of some hypoglycemic agents. Journal of Molecular Structure: THEOCHEM. 2009;897(1-3):73-82. [CrossRef]
- 12. Hale T, Abbey J. Drug transfer during breast-feeding. Fetal and Neonatal Physiology. Elsevier; 2017:239-248. e5.
- 13. Acharya PC, Marwein S, Mishra B, et al. Role of salt selection in drug discovery and development. Dosage Form Design Considerations. Elsevier; 2018:435-472. [CrossRef]
- 14. Serajuddin AT. Salt formation to improve drug solubility. Advanced Drug Delivery Reviews. 2007;59(7):603-616. [CrossRef]
- 15. Patel P, Ibrahim NM, Cheng K. The importance of apparent pKa in the development of nanoparticles encapsulating siRNA and mRNA. Trends in Pharmacological Sciences. 2021;42(6):448-460. [CrossRef]
- 16. Caldwell GW, Ritchie DM, Masucci JA, Hageman W, Yan Z. The new pre-preclinical paradigm: compound optimization in early and late phase drug discovery. Current Topics in Medicinal Chemistry. 2001;1(5):353-366. [CrossRef]
There are 16 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmacology and Pharmaceutical Sciences (Other), Clinical Chemistry |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | April 23, 2024 |
| Submission Date | January 25, 2024 |
| Acceptance Date | March 14, 2024 |
| Published in Issue | Year 2024 Volume: 4 Issue: 2 |
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