Olaparib: Analytical methods for the quantification in drug substance, pharmaceutical formulations and biological matrices

The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (OLA), which is approved for the treatment of BRCA1/2-mutated ovarian, breast, pancreatic, and prostate cancers, requires accurate and reliable quantification in drug substance, pharmaceutical formulations, and biological matrices, including urine, plasma, and tissues. Pharmaceutical quality control, pharmacokinetic evaluation, bioanalytical studies, stability assessment, and therapeutic drug monitoring all depend on robust analytical techniques. This review critically evaluates the reported analytical methods for OLA determination, including high-performance liquid chromatography (HPLC), high-performance thin-layer chromatography (HPTLC), liquid chromatography-tandem mass spectrometry (LC-MS/MS), ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS), and UV-Vis spectroscopy, with a focus on sensitivity, specificity, linearity, and validation parameters. The review also examines the influence of sample preparation and extraction techniques, such as protein precipitation, liquid-liquid extraction, and solid-phase extraction, on recovery, selectivity, and matrix-effect control during OLA analysis. While HPLC and UV-Vis spectroscopy remain valuable for routine pharmaceutical analysis, LC-MS/MS and UPLC-MS/MS have emerged as the most sensitive and selective methods for trace-level quantification in biological matrices. To achieve reliable, environmentally sustainable, and regulatory-compliant OLA quantification, this review also highlights current challenges and future perspectives in stability-indicating techniques, Green Analytical Chemistry (GAC) principles, Quality by Design (QbD)-assisted method development, and sustainable analytical strategies.