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

TL;DR

This paper presents a new chiral HPLC method for measuring talazoparib and its enantiomeric purity in cancer treatments.

Contribution

A novel chiral HPLC method using a Box–Behnken design for talazoparib quantification and enantiomeric purity determination is developed.

Findings

Efficient enantiomeric separation of talazoparib was achieved with a resolution exceeding 7.7 in 12 minutes.

The method showed high accuracy and precision with recovery values of 98%–102% and RSD under 2%.

The method was successfully applied to pharmaceutical formulations for enantiomeric purity control.

Abstract

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.

A design of experiments–based chiral HPLC method was developed for the enantiomeric separation and quantification of talazoparib in pharmaceutical formulations. Efficient resolution of the enantiomers (R

S
 > 7) was achieved within 12 min. The method was validated and successfully applied to tablet analysis, and its environmental sustainability was evaluated.

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