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

Abstract:

:A new methodology based on Nuclear Magnetic Resonance (NMR) was developed to determine 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 concentrations and their fraction bound (fb) reported in the literature. Based on these results, a protocol for a rapid calculation of fb of small molecules was established. The advantage of using plasma instead of purified recombinant proteins and the possibility of pool analysis to increase throughput were also evaluated. This novel methodology proved to be very versatile, cost-effective, fast and suitable for automation. As a plus, it contemporarily provides a quality check and solubility of the compound.

journal_name

J Pharm Biomed Anal

authors

Gallo M,Matteucci S,Alaimo N,Pitti E,Orsale MV,Summa V,Cicero DO,Monteagudo E

doi

10.1016/j.jpba.2019.01.049

subject

Has Abstract

pub_date

2019-04-15 00:00:00

pages

21-29

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(18)32370-7

journal_volume

167

pub_type

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