Validated LC-MS/MS method for the quantification of olaparib and abiraterone acetate in human plasma

Abstract

Background: Olaparib and Abiraterone acetate are approved in combination therapy for metastatic castration-resistant prostate cancer (mCRPC). Accurate and simultaneous quantification of these agents in plasma is crucial for pharmacokinetic assessment and drug–drug interaction studies. Method: A rapid, simple, and selective LC-MS/MS method was developed and validated for the simultaneous quantification of Olaparib (25–5000 ng/mL) and Abiraterone acetate (1.25–250 ng/mL) in human plasma. Protein precipitation using chilled acetonitrile was employed for plasma extraction, with Carbamazepine and Abiraterone-D4 as internal standards for Olaparib and Abiraterone acetate, respectively. Validation parameters—linearity, precision, accuracy, recovery, stability, and sensitivity were assessed in accordance with ICH M10, FDA, and EMA bioanalytical guidelines. Results and Discussion: The method exhibited excellent linearity (r² > 0.998) across the specified ranges. LLOQs were 25 ng/mL (Olaparib) and 1.25 ng/mL (Abiraterone acetate), representing improved sensitivity versus earlier assays. Recoveries were 93–99%, with intra- and inter-day precision <10% CV. Stability under bench-top, freeze–thaw, and long-term conditions remained within ±15%. A total run time of 6 min ensured high throughput and reduced solvent consumption. Conclusion: The validated LC-MS/MS method is robust, sensitive, and reproducible, and is well-suited to pharmacokinetic and drug–drug interaction studies in oncology research. This method is suitable for clinical pharmacokinetic and drug–drug interaction studies involving prostate cancer therapies.