title: Quantifying trifluoroacetic acid as a counterion in drug discovery by 19F NMR and capillary electrophoresis.
abstract: Drug discovery compounds are often isolated as salts of trifluoroacetate from preparative high performance liquid chromatography, which are then used for biological assays in order to assess their efficacy against the biochemical target of interest. It is, therefore, imperative to determine the TFA content in order to ascertain the correct formula weight and when required, to ensure that the TFA has been completely exchanged for another counterion in order to have superior pharmacokinetic properties and to avoid potential toxicity effects. In this paper, we present capillary electrophoresis and (19)F nuclear magnetic resonance methods for determining the TFA content of drug discovery compounds. Furthermore, these methods have been successfully applied in a high-throughput fashion, which is a key feature for general applicability in a pharmaceutical setting.
authors.affiliation: Department of Chemistry, Boehringer Ingelheim (Canada) Limited, Research and Development, 2100 Cunard Street, Laval, Quebec, Canada H7S 2G5. mlittle@lav.boehringer-ingelheim.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Little
authors.forename: Norman
authors.initials: N
authors.lastname: Aubry
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Beaudoin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goudreau
authors.forename: Steven R
authors.initials: SR
authors.lastname: LaPlante
mesh_terms: D002412:Cations; D015195:Drug Design; D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D015394:Molecular Structure; D009501:Neutron Activation Analysis / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014269:Trifluoroacetic Acid / Q000032:analysis* / Q000737:chemistry
chemical_list: D002412:Cations; D014269:Trifluoroacetic Acid