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Pharmacokinetic and metabolic analysis of an Alzheimer's disease therapeutic in rat serum via microfluidic CZE–MS
Biomedical Chromatography  (IF1.902),  Pub Date : 2021-09-13, DOI: 10.1002/bmc.5243
Zachary D. Kelley, Mark A. Lovell, Bert C. Lynn

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.