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优化对宏环的发现生物分析策略

Xing Zhang¹, Stephanie Dale², Yusi Cui²

¹Genentech Inc, DMPK, South San Francisco, CA, USA. zhanx239@gene.com.

Analytical and bioanalytical chemistry

|February 15, 2025

概括

开发一个强大的生物分析策略对宏环 (MCPs) 对于药物发现至关重要. 这项研究优化了样本提取,并利用有针对性的选择离子监测 (t-SIM) 来进行高通量MCP量化.

科学领域:

制药科学制药科学
分析化学分析化学
药物发现药物发现药物发现

背景情况:

宏环 (MCP) 是重要的治疗方法,但也带来了生物分析方面的挑战.
传统的测定与MCP的独特结构和ADME属性作斗争.

研究的目的:

开发和优化MCPs的高通量生物分析策略.
为了解决MCP药物发现的传统LC-MRM试验的局限性.

主要方法:

评估了十种样本提取方法,确定MeOH/ACN和FA的蛋白质沉是最优的.
在Orbitrap HRMS上评估了有针对性的选择性离子监测 (t-SIM) 和并行反应监测 (PRM).
与传统LC-MRM相比,t-SIM和PRM的灵敏度和性能进行了比较.

主要成果:

对于大多数MCP,蛋白质沉实现了80%的回收和90%的矩阵效应.
t-SIM表现出对MRM (LOQ 1-3 ng/mL) 的相似敏感性,并增加了灵活性.
优化的策略满足了各种生物矩阵的量化要求.

结论:

成功开发了一种针对MCP的优化,高通量生物分析策略.
t-SIM为MCP发现生物分析提供了一种敏感和灵活的替代传统LC-MRM.

关键词:

生物分析方法生物分析方法宏环类酸宏环类酸轨道飞行器高分辨率MS MS 定量分析是一种量化分析.样品的准备样品的准备

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