Synergistic dual-adsorbent solid-phase extraction for large-scale surveillance of citrinin: Critical risk-benefit paradox in red yeast rice supplements

Citrinin (CIT), a potentially carcinogenic mycotoxin, poses serious health threats, yet its accurate detection remains challenging due to severe matrix interference. This study developed a novel dual-layer SPE cartridge integrating graphitized carbon black (GCB) and mixed-mode anion-exchange (MAX) adsorbents to overcome limitations of conventional immunoaffinity columns and C 18 -SPE. The system selectively captures deprotonated CIT via anion exchange on MAX, while adsorbing planar pigments through π-π interactions on GCB. Following this efficient cleanup, the extracts were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method demonstrated high sensitivity (limit of detection: 0.05–0.5 μg/kg), negligible matrix effects (87.6 %-111 %), and excellent recovery (90.4 %-99.1 %) across diverse matrices. Large-scale surveillance ( n = 1616) identified red yeast rice products as the major contamination source, with 91.7 % exceeding EU limits. Critically, CIT strongly correlated with lovastatin (ρ=0.96, P < 0.001), indicating that red yeast rice (RYR) supplements introduce significant CIT co-exposure even at therapeutic lovastatin doses. These findings underscore the urgency of strengthening regulatory standards for RYR products. • Novel dual-adsorbent (GCB/MAX) SPE method was developed for the analysis of CIT. • First large-scale dietary CIT exposure assessment in China ( n = 1616). • Current CIT exposure (5.2–10.8 ng/kg b.w./day) was far below the safety threshold. • Over 90 % of RYR products (CIT>100 μg/kg) pose health risks at therapeutic doses. • Strong CIT-lovastatin correlation (ρ=0.96) reveals RYR risk-benefit paradox.