Monitoring and Managing of Ergot Alkaloids in Cereal Grains: A Comprehensive Analysis of Analytical Challenges, Sampling Uncertainty, and Processing for Food Safety.

Ergot alkaloids (EAs), toxic secondary metabolites produced by Claviceps purpurea, pose food and feed safety concerns for cereal grains, particularly rye and wheat. While EAs are most frequently associated with rye, their occurrence in other cereals has been increasingly reported across diverse regions. This review critically synthesizes current knowledge on the global occurrence, analytical detection, regulatory control, and processing behavior of EAs, with a particular focus on factors that limit data reliability and risk management. A defining challenge in EA monitoring is the highly heterogeneous distribution of ergot sclerotia and alkaloids within bulk grain, which introduces substantial sampling uncertainty that often exceeds analytical variability. Recent advances in comminution, spatial sampling models, and composite sampling strategies have improved representativeness, yet remain underemphasized relative to instrumental developments. Analytical methods have progressed from nonspecific HPLC approaches to high-throughput LC-MS/MS and LC-HRMS platforms, enabling sensitive, multi-analyte detection and epimer-specific quantification; however, persistent limitations, including matrix effects, limited availability of reference materials, and insufficient characterization of conjugated or matrix-bound EAs, continue to constrain comparability across studies. Regulatory approaches vary globally, with the European Union adopting chemical limits for total EAs, while other regions rely primarily on sclerotia-based grading. Climate change and evolving agricultural practices further complicate exposure assessment and mitigation. By integrating sampling theory, analytical chemistry, processing effects, and regulatory frameworks, this review provides a unified perspective on EA risk management and identifies priorities for future research, including harmonized sampling strategies and high-throughput analytical platforms capable of capturing both free and conjugated EA forms.