A process analytical strategy for monitoring toxicity-related alkaloid transformation in complex herbal decoctions using mid-infrared spectroscopy and an electronic tongue

Complex natural product processing involves dynamic compositional changes, yet rapid and standardized process characterization remains difficult when relying mainly on off-line laboratory analysis and sensory-based empirical judgment. To address this analytical need, Fuzi (Aconiti Lateralis Radix Praeparata), the processed lateral root of Aconitum carmichaelii Debx., and Si Ni Tang, a classical Chinese herbal formula containing Fuzi, were used as representative single-herb and formula decoction systems. An analytical framework was established in which high-performance liquid chromatography provided reference values for calibration and validation, the electronic tongue provided objective and reproducible digital responses related to sensory-based empirical evaluation, and mid-infrared spectroscopy supplied rapid molecular information on toxicity-related constituents. High-performance liquid chromatography was used to quantify six Aconitum alkaloids in the decoction samples, while electronic tongue responses and mid-infrared spectra were collected in parallel and modeled using chemometric methods. The decoction process showed a clear time-dependent conversion of diester diterpenoid alkaloids into the corresponding less toxic monoester diterpenoid alkaloids. Based on the chromatographic reference values, mid-infrared models provided reliable quantitative prediction of the target alkaloids, and the electronic tongue differentiated samples collected at different decoction time points according to their overall multi-sensor response patterns, thereby providing complementary information for rapid characterization of process states. Rather than replacing high-performance liquid chromatography for endpoint confirmation, this framework retains high-performance liquid chromatography as the reference method and extends evaluation from off-line endpoint testing to rapid process-oriented characterization of toxicity-related alkaloid transformation, providing a complementary analytical route for safety-related quality control of complex herbal decoctions.