pK(a) determinations by using a HPLC equipped with DAD as a flow injection apparatus

A semi-automated method to determine pK(a) values spectrophotometrically is described. The method uses the capabilities of a HPLC equipped with a diode array detector (DAD) as a flow injection apparatus. The advantages are low sample consumption, rapid sample throughput, high sensitivity, and precision. Experimental pK(a) values obtained for two model compounds, benzoic acid (similar to 4.0) and 2-aminopyridine (similar to 6.8), are consistent with literature values. Constant ionic strength was maintained for a wide pH range. Solubilized samples in non-aqueous solvents were also investigated. The weakening in pK, values, often seen when using non-aqueous solvents, was small (0.04-0.40 pH units) compared to conventional methods. (C) 1997 Elsevier Science B.V.