Panoramic contamination profiling and dietary exposure risk of plant growth regulators in medicinal and edible plants: A data modeling-driven MMSPE-UPLC-MS/MS platform.

Plant growth regulators (PGRs) are extensively deployed in medicinal and edible plants (MEPs) to enhance yields, yet their environmental persistence and potential ecotoxicological effects have raised significant public health concerns. However, current regulatory frameworks remain deficient in PGR-specific residue limits and cross-matrix surveillance tools. Herein, a data modeling-driven broad-spectrum analytical platform was engineered for comprehensive occurrence mapping and dietary exposure assessment of PGRs. Global optimization was achieved through simplex lattice mixture design combined with Derringer's desirability function, enabling all-inclusive mixed-mode solid-phase extraction (MMSPE) for 64 PGRs (Log Kow -3.80-5.68) across diverse polarity/ionization domains. Integrated with ultra-performance liquid chromatography-triple quadrupole-tandem mass spectrometry (UPLC-QqQ-MS/MS), the MMSPE-UPLC-MS/MS platform facilitated rapid quantification of multi-class PGRs (auxins, cytokinins, gibberellins, brassinosteroids, and growth retardants) in seven MEP matrices. Limits of quantification ranged from 0.016 to 14.392 μg/kg, with average recoveries of 68.93 %-118.07 % and relative standard deviations of 0.47 %-12.88 %. Among 140 commercial samples, 30 PGRs were detected (0.07-6392.80 μg/kg), revealing pervasive cross‑matrix contamination and elevated environmental exposure of both endogenous hormones and several synthetic PGRs. Hazard quotient/index-based risk assessments indicated generally acceptable population‑level exposure risk, but highlighted matrix‑dependent risk drivers, with tebuconazole, diuron and paclobutrazol dominating cumulative exposure in specific MEPs. Collectively, this work provided a powerful panoramic screening tool for uncovering cryptic chemical burden in complex herbal matrices, thereby establishing a scientific foundation for prioritizing control lists and refining toxicological benchmarks.