UPLC-MS/MS method for the determination of talazoparib in rat plasma and its pharmacokinetic study

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

“…We successfully developed and validated a simple, sensitive, robust, and reproducible UHPLC-MS/MS method for determining concentrations of the PARP inhibitor talazoparib in mouse plasma. Previous publications have reported LC-MS/MS assays that meet the sensitivity requirement for quantifying talazoparib in human liver microsomes [ 12 ], rat plasma [ 15 ], or human plasma [ 14 ] to support pharmacokinetics studies. However, these methods were developed in the context of studies in which relatively large volumes of biological fluid can be obtained (>50 μL), and thereby compromise application to the limited volumes that are available through repeat blood collection strategies in mice.…”

“…In an attempt to address this knowledge deficit, and shed light on possible drug drug interactions with talazoparib, we set out to develop and validate an analytical method for the determination of talazoparib in mouse plasma using UHPLC-MS/MS and implemented the method in a pharmacokinetic study utilizing wild-type mice and animal lacking ABCB1 and ABCG2. Although there are some reports of successful implementations of HPLC-MS/MS methods designed to detect talazoparib in arious matrices they are mostly optimized for rat or human plasma and therefore require larger samples sizes which are not feasible in mouse studies [ [12] , [13] , [14] , [15] ]. The current study aims to address the best possible method to address this issue and provides insight into the mechanisms underlying drug-drug interaction liabilities with talazoparib that further contribute to the safe and effective use of this clinically important drug in patients with cancer.…”

Development and validation of an integrated LC-MS/MS assay for therapeutic drug monitoring of five PARP-inhibitors

“…plasma which allows for rapid sample turnover. Various LC-MS/MS assays have been reported for the quantification of the different PARP-inhibitors alone [19][20][21][22][23][24][25] or in combination with other agents [13,[26][27][28][29], but not for the combined analysis of the five PARP-inhibitors for the specific purpose of TDM. Bioanalytical assays for TDM applications should be simple and fast, since these assays are widely used for routine clinical care.…”