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Physicochemical Profiling of Sartans: A Detailed Study of Ionization Constants and Distribution Coefficients
Author(s) -
Tosco Paolo,
Rolando Barbara,
Fruttero Roberta,
Henchoz Yveline,
Martel Sophie,
Carrupt PierreAlain,
Gasco Alberto
Publication year - 2008
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200890051
Subject(s) - chemistry , lipophilicity , candesartan , valsartan , irbesartan , potentiometric titration , chromatography , losartan , partition coefficient , capillary electrophoresis , analytical chemistry (journal) , angiotensin ii , stereochemistry , organic chemistry , ion , biochemistry , medicine , receptor , alternative medicine , pathology , blood pressure , radiology
A detailed investigation of the ionization and lipophilicity profiles of selected sartans (valsartan, losartan, irbesartan, candesartan, candesartan cilexetil), a class of antihypertensives commonly used in therapy, is presented. The p K a macroconstants were determined by integrated potentiometry, capillary electrophoresis, and UV spectrophotometry. The measured p K a macroconstants were connected with the ionizable centers present in each molecule with the aid of model compounds. Potentiometric titrations with the GLpKa apparatus were performed to determine the distribution profile (log D vs. pH) of valsartan, while the shake‐flask procedure was used to characterize the distribution profile of the other compounds. Valsartan showed a lipophilicity profile consistent with the presence of two acidic centers. Losartan and irbesartan, which contain one acidic and one basic center, displayed the classical bell‐shaped profile of ordinary ampholytes. By contrast, a more complex situation emerged in the case of candesartan, due to the large number of ionization equilibria involved. The low solubility of candesartan cilexetil, together with the ease of hydrolysis of the ester moiety, prevented a successful investigation of its ionization and lipophilicity profiles.