Nonlogarithmic titration curves may be used to determine thermodynamic dissociation constants in addition to measuring the purity of the substance titrated and estimating the accuracy of the data. Equations are derived and methods pro osed for carrying out these determinations with any monoprotic species (definecf here as an acid or base with an independently dissociating hydrogen). A distinct advantage of this method is that dissociation constants may be determined for titrations that begin at a pH past half neutralization. Sample curves are presented to show the effect of incorrect measurement of pH. Methods are also given for the determination of the urity and dissociation constants of polyprotic species with overlapping pK's. T i e usefulness of the method is demonstrated by the calculated values reported for demethylchlortetracycline, 4-epi-anhydrotetracycline, 6demethylgriseofulvin, phthalic acid, succinic acid, ethylenediamine, and 1,4-butanediamine.
N THE past few years several new pH meters I have come into common use. These instruments are considerably more precise than earlier models and consequently make i t possible to determine dissociation constants with greater accuracy than previously obtainable. The use of nonlogarithmic titration curves, as proposed here, will give highly accurate results in addition to a measure of the purity of the substance titrated and an estimate of the accuracy of the data.
A survey of the pharmaceutical literature shows that most dissociation constants are determined by methods which are modifications of that described by Parke and Davis (1). These authors used hydrogen ion binding curves to determine the apparent dissociation constants for a variety of mono-and polyprotic acids and bases. Identical volumes of sample solution and blank were titrated with a strong titrant over the pH range 2-12. The curves of these two titrations were plotted on a graph having pH as the abscissa and the amount of titrant added as the ordinate. A third curve, the difference curve, was then drawn with the units of the ordinate being the differences in milliliters of titrant required for the sample and blank to reach the same pH. Previously prepared transparent masks on which the standard curve has been drawn and the point of inflection marked are then fitted to the difference curve.
Since "any titratable group produces an inflection having the same shape regardless of its