A Design of Experiments-Based Chiral HPLC Method for the Quantification of Talazoparib and Enantiomeric Purity Determination in Pharmaceutical Formulations.

Talazoparib is an oral inhibitor of the polyadenosine 5'-diphosphoribose polymerase enzymes used for the treatment of adults with deleterious or suspected deleterious germline BRCA-mutated, human epidermal growth factor receptor 2-negative, locally advanced, or metastatic breast cancer. A novel chiral HPLC method was proposed for the enantiomeric separation and quantification of talazoparib. Chiral separation was performed in a reversed-phase mode on a Chiralpak IC (4.6 × 250 mm, 5 μm) column using a simple mobile phase consisting of 0.2% perchloric acid in water:acetonitrile (60:40, v/v). A Box-Behnken design was used for the optimization of chromatographic parameters, and the enantiomeric separation was obtained within 12 min with a resolution value exceeding 7.7. The method was validated with respect to specificity, linearity, accuracy, precision, and robustness. The accuracy and precision of the method were satisfactory, with intraday and interday recovery values of 98%-102% and relative standard deviation values less than 2%. The method was used for the enantiomeric purity control of talazoparib in pharmaceutical formulations, which is crucial for patient safety and therapeutic efficacy.