title: pH-Metric log K calculations of famotidine, naproxen, nizatidine, ranitidine and salicylic acid.
abstract: The octanol/water partition coefficient (log K) is one of the most commonly used parameters in structure-activity relationships in many areas such as drug design (including pesticides), pharmacokinetics, anesthesiology, environmental sciences, toxicology, bioaccumulation and predicting skin permeability as a predictive parameter. log K is generally determined using shake flask method, but the possibility of calculating log K using pH-metric titrations and half neutralization points is demonstrated in this study. The potentiometric pH titration technique has been developed as an automatic technique for log K determination but it can be achieved by manual titrations. This technique uses the pKa of the substance. The pKa of the substance shifts pK'a when the titration is repeated in the presence of octanol. log K value of the substance can be determined using pKa, pK'a values and relevant equation. The aim of the study was to determine the log K values of a series of compounds using pH-metric titrations and to compare pH-metric log K determination results with the other methods. The log K values of famotidine, naproxen, nizatidine, ranitidine and salicylic acid were determined using both shake flask method and potentiometric titrations. Their log K values were also calculated theoretically using computer program and all results were compared. The pH-metric log K values were found to be close to the shake flask method results. This method was found to be useful for the determination of log K values as it provides a high degree of accuracy even in the presence of titratable impurities in the solution.
authors.affiliation: University of Gazi, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey. tunc@tr.net
authors.forename: T
authors.initials: T
authors.lastname: Degim
authors.forename: V
authors.initials: V
authors.lastname: Zaimoglu
authors.forename: C
authors.initials: C
authors.lastname: Akay
authors.forename: Z
authors.initials: Z
authors.lastname: Degim
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D000897:Anti-Ulcer Agents / Q000737:chemistry*; D001241:Aspirin / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003201:Computers; D015738:Famotidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009288:Naproxen / Q000737:chemistry; D016567:Nizatidine / Q000737:chemistry; D011899:Ranitidine / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D009288:Naproxen; D015738:Famotidine; D011899:Ranitidine; D016567:Nizatidine; D001241:Aspirin