Exploring pharmacokinetics of talazoparib in ABCB1/ABCG2-deficient mice using a novel UHPLC-MS/MS method

• Published in: Heliyon Vol. 9; no. 11; p. e20972
• Main Authors: Talebi, Zahra, Garrison, Dominique A., Eisenmann, Eric D., Parmar, Kalindi, Shapiro, Geoffrey I., Rudek, Michelle A., Sparreboom, Alex, Jin, Yan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2023; Elsevier
• Subjects: ABC transporters; Mouse plasma; Pharmacokinetics; Talazoparib; UHPLC-MS/MS; ABC transporters; Talazoparib; UHPLC-MS/MS; Pharmacokinetics; Mouse plasma
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e20972

A rapid, sensitive, and simple UHPLC-MS/MS method for the determination of the PARP inhibitor talazoparib in mouse plasma was developed and validated using [13C,2H4]-talazoparib as an internal standard (IS). The assay procedure involved extraction of talazoparib and the IS from plasma using a single-step deproteination and separation of the analytes was achieved on an ACQUITY UPLC RP18 HSS T3 column with a mobile phase gradient at a flow rate of 0.4 mL/min in a run time of 5 min. The calibration curve was linear (r2 > 0.99) over the concentration range of 0.5–100 ng/mL, and 10-fold dilution of samples could be accurately quantitated. The matrix effect and mean extraction recovery for talazoparib were between 93.7-109% and 87.7–105%, respectively. Precision and percent bias of quality control samples were always less than ±15%, indicating reproducibility and accuracy of the method. Talazoparib demonstrated bench-top stability at room temperature for 6 h, auto-sampler and reinjection stability at 4 °C for at least 24 h, and no significant degradation was observed after three freeze-thaw cycles. The developed method was successfully applied to pharmacokinetic studies involving serial blood sampling after oral administration of talazoparib to wild-type mice and animals with a genetic deficiency of the efflux transporters ABCB1 (P-gp) and ABCG2 (BCRP). Together, our results demonstrate the successful development of a suitable analytical method for talazoparib in mouse plasma and suggest that mice are a useful model to evaluate transporter-mediated drug-drug interactions involving therapy with talazoparib.