Application of a microfluidic CE* device for CZE‐MS allows for fast, rapid, and in‐depth analysis of large sample sets. This microfluidic CZE‐MS device, the 908 Devices ZipChip, involves minimal sample preparation and is ideal for small cation analytes, such as alkaloids. Here, we evaluated the microfluidic device for the analysis of alkaloids from Lobelia cardinalis hairy root cultures. Extracts from wild‐type, transgenic, and selected mutant plant cultures were analyzed and data batch processed using the mass spectral processing software MZmine2 and the statistical software Prism 8. In total 139 features were detected as baseline resolved peaks via the MZmine2 software optimized for the electrophoretic separations. Statistically significant differences in the relative abundance of the primary alkaloid lobinaline (C27H34N2), along with several putative “lobinaline‐like” molecules were observed utilizing this approach. Additionally, a method for performing both targeted and untargeted MS/MS experiments using the microfluidic device was developed and evaluated. Coupling data‐processing software with CZE‐MS data acquisition has enabled comprehensive metabolomic profiles from plant cell cultures to be constructed within a single working day.

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.

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