Talebi Zahra, Garrison Dominique A, Eisenmann Eric D, Parmar Kalindi, Shapiro Geoffrey I, Rudek Michelle A, Sparreboom Alex, Jin Yan
Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Heliyon. 2023 Oct 13;9(11):e20972. doi: 10.1016/j.heliyon.2023.e20972. eCollection 2023 Nov.
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 [C,H]-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 ( > 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.
建立了一种快速、灵敏且简便的超高效液相色谱-串联质谱法（UHPLC-MS/MS），以[C,H]-他拉唑帕利作为内标（IS），用于测定小鼠血浆中的PARP抑制剂他拉唑帕利，并进行了方法验证。分析步骤包括通过一步脱蛋白从血浆中提取他拉唑帕利和内标，在ACQUITY UPLC RP18 HSS T3柱上实现分析物的分离，流动相采用梯度洗脱，流速为0.4 mL/min，运行时间为5分钟。校准曲线在0.5-100 ng/mL的浓度范围内呈线性（>0.99），样品10倍稀释后仍可准确定量。他拉唑帕利的基质效应和平均提取回收率分别在93.7-109%和87.7-105%之间。质量控制样品的精密度和偏差百分比始终小于±15%，表明该方法具有重现性和准确性。他拉唑帕利在室温下具有6小时的台式稳定性，在4°C下自动进样器和再进样稳定性至少为24小时，经过三个冻融循环后未观察到明显降解。所建立的方法成功应用于药代动力学研究，该研究涉及对野生型小鼠以及外排转运体ABCB1（P-糖蛋白）和ABCG2（乳腺癌耐药蛋白，BCRP）基因缺陷动物口服他拉唑帕利后的连续采血。总之，我们的结果表明成功开发了一种适用于测定小鼠血浆中他拉唑帕利的分析方法，并表明小鼠是评估涉及他拉唑帕利治疗的转运体介导的药物-药物相互作用的有用模型。
