Bioanalytical Methods for Poly(ADP-Ribose) Polymerase Inhibitor Quantification: A Review for Therapeutic Drug Monitoring

Background:Therapeutic drug monitoring (TDM) of poly(ADP-ribose) polymerase inhibitors (PARPis) is an exploratory practice aimed at improving the quality of treatment through personalized therapy. Currently, there are 4 European Medicines Agency-approved and US Food and Drug Administration-approved PARPis available clinically whose quantification requires validated analytical methods: olaparib, niraparib, rucaparib, and talazoparib. The purpose of this literature review was to highlight the pharmacological features of PARPis that could support their TDM practice and provide a detailed discussion of the available liquid chromatography coupled with tandem mass spectrometry methods for their quantification.Methods:Using several Medical Subject Heading terms, the literature was searched using several research engines, including SciFinder, Web of Science, Google Scholar, and PubMed, to find articles published before August 2022.Results:Exposure-efficacy and exposure-safety profiles, drug-drug interactions, and hepatic/renal impairment of PARPis provide the potential rationale to monitor their concentrations through TDM. Several bioanalytical methods for their quantification have been reported and compared, and a great deal of heterogeneity has been found among methods, regarding both their analytical and regulatory aspects.Conclusions:In addition to reducing toxicity and increasing the efficacy of PARPis therapy, TDM could be beneficial to thoroughly investigate the exposure-response relationships of PARPis and to establish pharmacokinetic thresholds for clinical decisions. Based on the comparison of published bioanalytical methods, their transferability and validation both play a key role in method selection. For future use in clinical TDM, we anticipate that bioanalytical methods should address every analytical need more thoroughly and should be validated with standardized guidelines.