ABSTRACT Monotherapy for the aggressive triple‐negative breast cancer often yields limited efficacy, prompting the emerging strategy of exploring combination therapies to target multiple pathways. Therefore, developing and validating a simple, rapid, and sensitive assay to simultaneously quantify the drugs in bio‐matrices is particularly crucial. In the present study, a liquid chromatography‐tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of nebivolol (NBV), dasatinib (DAS), and devimistat (CPI), which may be used for triple‐negative breast cancer (TNBC) therapy. The individual deuterated compounds served as the respective internal standards (IS). An isocratic mobile phase comprising water with 0.1% formic acid (aqueous phase) and acetonitrile (organic phase) at a ratio of 3:7, v/v, and electrospray ionization (ESI) in positive mode was utilized to monitor the three drugs with transitions m / z of 406/151 for NBV, 488/401 for DAS, and 389/91 for CPI. The lower limit of quantification (LLOQ) was 0.5 ng/mL for all analytes. The linearity, selectivity, sensitivity, accuracy, precision (intraday and interday), matrix effect, and recovery were all within acceptable limits. The developed method was successfully applied to simultaneously establish the pharmacokinetic (PK) profiles of the three analytes in rats and was demonstrated as suitable for analyzing serial plasma samples.
Li et al. (Sun,) studied this question.