The 2018 FDA Guidance for the Validation of Bioanalytical Methods requires an assessment of the impact of the presence of coadministered drugs on the analytical measurement and stability of novel drug candidates. GLP-compliant methods were developed and validated in support of a clinical study that featured co-administration of itraconazole, paroxetine, cimetidine, moxifloxacin, and valproic acid with a proprietary drug candidate. Various methods involving protein-precipitation and liquid-liquid extraction were employed utilizing direct-analysis or dilution of supernatant as well as evaporation with nitrogen followed by reconstitution of analyte in organic solvent.