通过交叉矩阵校准和贝叶斯等级建模,提高血中异生菌的定量分析
Nipunika H Godage1,2,3, Song S Qian4, Erasmus Cudjoe5
1Department of Chemistry and Biochemistry, College of Natural Sciences and Mathematics, The University of Toledo, Toledo, Ohio 43606, United States.
这项研究引入了贝叶斯层次模型来纠正血蛋白结合变异,使生物流体分析的成本有效的校准策略能够使用易于获得的血类型.
科学领域:
- 分析化学 分析化学
- 药理动力学 药理动力学
- 生物分子分析
背景情况:
- 精确量化血中小分子对于生物监测和药理动力学研究至关重要.
- 矩阵效应和物种间血蛋白结合 (PPB) 在生物分析方法验证中引入了变异性.
- 传统的矩阵匹配校准需要特定的,往往昂贵的等离子体类型,如人体等离子体.
研究的目的:
- 为生物流体分析制定一个具有成本效益的校准策略.
- 为了减轻因不同物种之间血蛋白结合引起的测量偏差.
- 探索交叉矩阵校准和贝叶斯等级建模 (BHM) 对于外来生物量化的实用性.
主要方法:
- 使用生物相容固体相微提取 (SPME) 与液态染色体质谱学 (LC-MS) 结合的有针对性的定量方法的开发.
- 对人类,牛,老鼠和子等离子体的绝对矩阵效应的评估.
- 应用贝叶斯层次模型 (BHM) 来计算PPB的分析物特定校正因数.
主要成果:
- 生物相容的SPME最大限度地减少了共提取干扰,绝对矩阵效应在96%-108%之间.
- 使用牛血进行交叉矩阵校准不足以准确测量人类血.
- 在人体血中,BHM成功地纠正了来自不同校准策略的测量偏差.
结论:
- BHM提供了一种有效的策略来纠正血蛋白结合变异,使不同类型的血能够准确量化.
- 利用可访问的血来源 (例如,牛) 来优化方法可以降低成本,提高生物分析研究的效率.
- 这种方法为生物监测和药理动力学研究提供了显著的优势,这些研究需要强大的和经济的校准方法.
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