ABSTRACT The FDA has approved Talazoparib and Enzalutamide for metastatic castration‐resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) gene mutations, based on the TALAPRO‐2 Phase 3 trial. This study developed and validated an LC‐MS/MS method for simultaneous quantification of Talazoparib and Enzalutamide in rat plasma using Apalutamide as the internal standard. Chromatographic separation was achieved with a 70:30 (v/v) acetonitrile–0.1% formic acid system, 10 min runtime, and 1.0 mL/min flow rate. Retention times were 4.13 min (Talazoparib), 5.31 min (Enzalutamide), and 7.89 min (Apalutamide). Detection was performed in positive ionization mode using MRM transitions: m / z 381.35 → 240.56, 465.44 → 305.24, and 478.44 → 285.10, respectively. The method was linear over 0.05–2 ng/mL for Talazoparib and 4–160 ng/mL for Enzalutamide ( r 2 > 0.999). Accuracy and precision were within ±15%–20%, and recovery exceeded 98%. In pharmacokinetic studies on male Wistar rats, Talazoparib showed a C max of 0.88 ng/mL at 3 h and an AUC 0− t of 20 ng·h/mL, while Enzalutamide exhibited a C max of 76.18 ng/mL at 1 h and an AUC 0− t of 1702 ng·h/mL; both had 24 h half‐lives. The validated method enables sensitive, rapid, and reliable bioanalysis for preclinical pharmacokinetic evaluation.
Guntupalli et al. (Tue,) studied this question.