Yang, Linhong and Skolnik, Suzanne (2023) Avoid missing pKas: high throughput workflow using solution pH-metric in tandem with UV-metric measurements. Journal of pharmaceutical and biomedical analysis, 234 (115530). ISSN 1873-264X; 0731-7085

Abstract

We describe a new high throughput automated pKa workflow using potentiometry starting with 10 mM DMSO stock (solution pH-metric). Two approaches using either neat DMSO stock solution or removal of DMSO were evaluated with different sample amounts and cosolvent schemes. These were validated against traditional potentiometric measurements for optimal conditions. Further, we detail how high throughput solution pH-metric experiments are performed in tandem with established UV-metric measurements to capitalize on the advantages of both approaches. This new workflow maintains the sample and time savings required for measuring large number of samples in a drug discovery setting, while avoiding “missing pKas” due to lack of sufficient UV chromophores. The combination of the two assays is key to tackle the challenges of low solubility, overlapping pKas, and assignment of pKas for SAR understanding.

Item Type:	Article
Date Deposited:	04 Jul 2023 00:45
Last Modified:	04 Jul 2023 00:45
URI:	https://oak.novartis.com/id/eprint/49084