Determination of dissociation constants of weak acids by feedback-based flow ratiometry Original Research Article

We applied the principle of feedback-based flow ratiometry, originally developed for continuous titrations, to the determination of acid dissociation constants (Ka). The titrant (NaOH) flow rate FB was varied in response to a control voltage Vc from a controller, while the total (titrant+titrand) flow rate FT was held constant. The titrand was aspirated to the flow system at the flow rate of FT−FB, and mixed with the titrant at the confluence point. Downstream, the pH of the mixed solution was measured with a glass electrode. Initially, Vc (thus FB) was ramped upward linearly. At the instant the detector sensed the half equivalence point, Eq1/2, where the buffer capacity is maximum, the algorithm reversed the ramp direction of Vc downwards. When Eq1/2 was sensed again, the algorithm reversed the ramp direction of Vc again, upwards. By repeating these processes automatically, time utilization efficiency of the procedure was improved by scanning Vc only in the range of interest. When the Vc scan range was thus constrained, the pH values corresponding to either a maximum or minimum in Vc, were equal to the pKa of the analyte. The pKa values thus obtained for various n-alkyl carboxylic acids and phosphoric acid agreed well with the literature. High throughput (ca. 26 s per determination) was attainable with reasonable precision (R.S.D.<3%).