Alkaline hydrolysis coupled with array gas membrane separation device and HPLC-FL for the determination of metformin...

A heat-assisted array gas membrane separation strategy coupled with High-Performance Liquid Chromatography Fluorescence detection was developed for sensitive determination of metformin based on an indirect quantification principle. Metformin was converted in situ under alkaline heating into volatile dimethylamine (DMA), which was selectively transferred through a hydrophobic Polytetrafluoroethylene membrane and trapped in an acidic acceptor solution, followed by pre-column derivatization with dansyl chloride to enable fluorescence detection. Mechanistic investigations confirmed DMA formation and identified additional alkaline degradation products (guanylurea-type intermediate, urea and guanidine) by HILIC and High-Resolution Time-of-Flight Mass Spectrometry, providing the chemical basis for the indirect workflow. Computational fluid dynamics simulations indicated focused headspace flow across the membrane (57.6% of total flow), negligible trans-membrane pressure (<0.5 Pa) and a moderated membrane temperature (∼49 °C) under an 80 °C heat source, rationalizing efficient transfer and reduced secondary volatilization. Key parameters were optimized, including heating time, absorption configuration, derivatization conditions. Under optimized conditions, the method was linear over 20-100 μg/mL (R = 0.9924) with a limit of detectionof 0.002 μg/mL (S/N = 3). Applicability was demonstrated in corn silk tea and sour jujube kernel tea, giving recoveries of 89.2-99.3% at 100 μg/mL and 95.4-102.0% across spiking levels, with no evident chromatographic interferences. The Alkaline Hydrolysis-Array Gas Membrane Separation-HPLC-FL approach integrates conversion, membrane-based separation and fluorescence derivatization, offering an efficient and solvent-minimized option for routine screening of metformin adulteration in complex matrices.