Sensitive, high-throughput methods for pharmacokinetic (PK) profiling are essential for potential therapeutics during critical stages of clinical trials. The application of a microfluidic capillary zone electrophoresis mass spectrometry (CZE–MS) method for PK profiling allows for rapid, sensitive and in-depth analysis of multiple samples within a short timeframe. Here, a CZE–MS approach for PK analysis was compared with a traditional UHPLC–MS approach when analyzing serum extracts from rats treated with a potential Alzheimer's disease therapeutic, BNC-1. Resulting PK data generated from both methods displayed statistical similarities. Additionally, the separation efficiency attributed to the use of the CZE–MS method provided substantial metabolic regulation data that was not apparent in the UHPLC–MS method. Additionally, the coupling of the CZE–MS method to the data processing software, MZmine2, was used to monitor changes in metabolism and observe putative BNC-1-derived metabolites. The ability to perform fast analyses without sacrificing sensitivity or metabolic information suggests that this CZE–MS method is ideal for metabolomics-inclusive, high-throughput PK profiling.

中文翻译：

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通过微流体 CZE-MS 对大鼠血清中阿尔茨海默病治疗剂的药代动力学和代谢分析

用于药代动力学 (PK) 分析的敏感、高通量方法对于临床试验关键阶段的潜在治疗至关重要。将微流体毛细管区带电泳质谱 (CZE-MS) 方法应用于 PK 分析允许在短时间内对多个样品进行快速、灵敏和深入的分析。在这里，在分析用潜在的阿尔茨海默病治疗剂 BNC-1 治疗的大鼠的血清提取物时，将用于 PK 分析的 CZE-MS 方法与传统的 UHPLC-MS 方法进行了比较。两种方法产生的 PK 数据显示出统计学上的相似性。此外，归因于使用 CZE-MS 方法的分离效率提供了大量的代谢调节数据，这在 UHPLC-MS 方法中并不明显。此外，CZE-MS 方法与数据处理软件 MZmine2 的耦合用于监测代谢变化并观察推定的 BNC-1 衍生代谢物。在不牺牲灵敏度或代谢信息的情况下进行快速分析的能力表明，这种 CZE-MS 方法非常适合代谢组学、高通量 PK 分析。