A novel method using nuclear magnetic resonance for plasma proteinbinding assessment in drug discovery programs.

By Gallo, Mariana; Matteucci, Sara; Alaimo, Nadine; Pitti, Erica; Orsale, Maria V.; Summa, Vincenzo; Cicero, Daniel O.; Monteagudo, Edith
From Journal of Pharmaceutical and Biomedical Analysis (2019), 167, 21-29. Language: English, Database: CAPLUS, DOI:10.1016/j.jpba.2019.01.049

A new methodol. based on NMR was developed to det. plasma protein binding (PPB) of drug candidates in drug discovery programs. A strong correlation was found between the attenuation of NMR signals of diverse drugs in the presence of different plasma concns. and their fraction bound (fb) reported in the literature. Based on these results, a protocol for a rapid calcn. of fb of small mols. was established. The advantage of using plasma instead of purified recombinant proteins and the possibility of pool anal. to increase throughput were also evaluated. This novel methodol. proved to be very versatile, cost-effective, fast and suitable for automation. As a plus, it contemporarily provides a quality check and soly. of the compd.