This study describes the adaptation of conventional titrimetric and spectrophotometric techniques to a microscale for the determination of drug ionization constants (pKa) and partition coefficients (log P). The apparatus for determining pKa and compound purity (or equivalent weight) consists of a three-port conical glass microvial maintained at 25 degrees C, a pH microelectrode, and a microinjection pump equipped with a 10 microL gastight syringe for titrant delivery. Sample mixing and protection from atmospheric CO2, which is particularly important at the microscale, is accomplished using a fine stream of water-saturated N2 bubbles. Simple titrimetric procedures combined with ionic equilibria models which allow the accurate determination of pKa and purity (or equivalent weight) using sample sizes in the microgram range and solution volumes of 10-100 microL were developed and validated using acetic acid and tromethamine. Simultaneous determinations of pKa, purity or equivalent weight, and octanol/water partition coefficient were shown to be possible from a single sample of a test solute by adapting the pH-metric technique to a microscale. Using benzoic acid as a model compound, a pKa of 4.24 and octanol/water partition coefficient of 64 were obtained, in close agreement with the literature values. The principles employed in titrimetric analysis were also applied to demonstrate the spectrophotometric determination of benzoic acid's pKa and partition coefficient using only 6 micrograms of compound. The microscale titration method was then used to determine the two pKa values of an "unknown" diprotic acid containing a carboxyl and an aromatic SH group. The phenyl thiol pKa was confirmed using the microscale spectrophotometric procedure.