title: A potentially simpler approach to measure aqueous pKa of insoluble basic drugs containing amino groups.
abstract: The aqueous pK values ((w/w)pK(a)) of several sparingly water-soluble drugs with amino groups have been calculated from pK values determined in several methanol/water mixtures ((s/s)pK(a)) by means of the Yasuda-Shedlovsky equation and by a linear equation that relates ((w/w)pK(a)) of amino compounds with ((s/s)pK(a)) obtained in any particular methanol/water mixture. Parameters of this last equation for amino compounds can be easily calculated from solely the methanol content of the solvent. Results from both approaches are consistent. However, Yasuda-Shedlovsky equation requires several ((s/s)pK(a)) determinations in solutions with different methanol content and can be used only from measurements in solutions with a maximum methanol content of about 65% in weight. In contrast, the linear proposed equation allows a very good estimation of ((w/w)pK(a)) from only one experimental ((s/s)pK(a)) value, and it permits this estimation from ((s/s)pK(a)) determined in a solution very rich in methanol. Therefore, it is suitable for very insoluble compounds. The examined amino compounds cover a wide range ((w/w)pK(a)) from 6.7 to 10.6, which have been estimated from experimental ((s/s)pK(a)) values in the whole composition range. In all instances consistent and satisfactory results have been achieved.
authors.affiliation: Departament de Química Analítica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Ruiz
authors.forename: Clara
authors.initials: C
authors.lastname: Ràfols
authors.forename: Martí
authors.initials: M
authors.lastname: Rosés
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bosch
mesh_terms: D000928:Antidepressive Agents / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D011199:Potentiometry / Q000379:methods; D012995:Solubility / Q000187:drug effects; D014867:Water / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D014867:Water