The First Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, PR China.
Medical College of Henan University of Science and Technology, 471003 Luoyang, PR China.
J Pharm Biomed Anal. 2020 Jan 5;177:112850. doi: 10.1016/j.jpba.2019.112850. Epub 2019 Aug 31.
In the present study, an accurate and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of plasma talazoparib concentration in rats was developed and established. The purpose of chromatographic separation of talazoparib and the internal standard (bosutinib) was achieved on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 μm) column with a flow rate of 0.40 mL/min, using a gradient elution with acetonitrile and 0.1% formic acid in water as the mobile phase. The detection was performed on a XEVO TQ-S triple quadrupole tandem mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring (MRM) mode with the precursor-to-product ion transitions of m/z 381.3 → 285.2 for talazoparib and m/z 530.2 → 141.2 for bosutinib (IS), respectively. The method was linear over the range of 0.5-200 ng/mL for talazoparib. The accuracies and precisions of intra- and inter-day were all within the acceptance limits, and no matrix effect was observed in this method. The validated method was further employed to a pharmacokinetic study of talazoparib after oral treatment with 0.2 mg/kg talazoparib to rats.
在本研究中，建立并确立了一种灵敏、准确的超高效液相色谱串联质谱法（UPLC-MS/MS），用于测定大鼠血浆中他拉唑帕尼的浓度。采用 Acquity BEH C18（2.1mm×50mm，1.7μm）柱，以乙腈和 0.1%甲酸水溶液为流动相，在 0.40mL/min 的流速下进行色谱分离，实现了他拉唑帕尼和内标（波舒替尼）的分离。采用电喷雾电离接口，在正离子多反应监测（MRM）模式下，对 XEVO TQ-S 三重四极杆串联质谱仪进行检测，他拉唑帕尼的母离子-子离子转换为 m/z 381.3→285.2，内标（波舒替尼）的母离子-子离子转换为 m/z 530.2→141.2。该方法在 0.5-200ng/mL 范围内对他拉唑帕尼呈线性。日内和日间精密度和准确度均在可接受范围内，且该方法无基质效应。该验证方法进一步用于研究大鼠口服 0.2mg/kg 他拉唑帕尼后的他拉唑帕尼药代动力学。
