Biopharmaceutical Studies of Thiazide Diuretics. I. Determination of pK_a Values and Partition Coefficients of Thiazide Diuretics

Abstract

The overlapping pK_a values of several thiazide diuretics were determined at 25±2°C by an improved spectrophotometric method. The absorbance of the ionized form cannot be measured directly due to the overlapping, but can be calculated from the data obtained experimentally in a region where overlapping does not occur. This method can be used to determine the pK_a values of drugs to which the usual means available for measurement of the ionization constants cannot be applied. The partition coefficients of these drugs between water and n-octanol were also determined at pH 2-10, and the behavior on an adsorption chromatographic column was studied. The pH profiles of both characteristics were very similar.