Medicine Design, Pfizer Worldwide Research & Development, Pfizer Inc., Groton, CT 06430, USA.
Medicine Design, Pfizer Worldwide Research & Development, Pfizer Inc., Cambridge, MA 02139, USA.
Bioanalysis. 2024 Jun 2;16(11):545-555. doi: 10.1080/17576180.2024.2349421. Epub 2024 Jun 10.
The purpose of this work was to determine the feasibility of supporting a clinical microdose study for PF-06882961 (danuglipron), an oral small molecule agonist of the GLP-1 receptor, by LC-MS/MS. Statistical instrument parameter optimization using response surface methodology was employed to develop a LC-MS/MS method for the analyte, PF-06882961. An LC-MS/MS method was developed and validated to support a proof of concept microdose pharmacokinetics preclinical study in monkeys, administered PF-06882961 (0.005 mg total, average dose = 0.0007 mg/kg) via intravenous bolus injection. The present study demonstrated the feasibility of analyzing human microdose plasma samples for PF-06882961 by LC-MS/MS, instead of accelerator mass spectrometry, thereby reducing cost and eliminating synthesis and exposure to C labeled material.
这项工作的目的是确定通过 LC-MS/MS 支持 PF-06882961（danuglipron）临床微剂量研究的可行性，PF-06882961 是一种 GLP-1 受体的口服小分子激动剂。采用响应面法对统计仪器参数进行优化，开发了用于分析物 PF-06882961 的 LC-MS/MS 方法。开发并验证了一种 LC-MS/MS 方法，以支持在猴子中进行概念验证性微剂量药代动力学临床前研究，通过静脉推注给予 PF-06882961（总 0.005mg，平均剂量= 0.0007mg/kg）。本研究证明了通过 LC-MS/MS 分析人微剂量血浆样品中的 PF-06882961 的可行性，而不是加速器质谱法，从而降低了成本，并消除了对 C 标记材料的合成和暴露。
