The acid-base behavior of benzodiazepines was studied by using a new technique GL-pK(a) in different ethanol water [up to 50 % (v/v) ethanol] and methanol water [up to 50 % (v/v) methanol] mixtures and at different temperatures. The ionic strength was maintained using potassium chloride. The primary goal of this work was to study the effect of different factors like dielectric constant, temperature, and ionic strength on the dissociation constant of benzodiazepines in detail as these are widely used in every day medical practice and forensic and clinical investigations. Potentiometric titrations were performed for determination of the pK values. This technique was found to be convenient, accurate, and easily applicable. The pK values obtained were in good agreement with literature values within experimental error.