Paper-immobilized liquid-phase microextraction for direct paper spray mass spectrometry and immuno-detection of atropine in baby food, buckwheat cereals, and edible oils at regulatory levels

Background: Atropine is a strictly regulated natural toxin. Monitoring for atropine is thus important, but often expensive and time-consuming. Moreover, the range of relevant matrices, and corresponding differences in required detection limits for atropine vary. Therefore, we developed a more simplified and affordable method, combining immunodetection and mass spectrometry to detect atropine in buckwheat, canola oil, and baby cereals at regulatory levels. Results: In this method, atropine is selectively enriched on paper using a dual-paper-immobilized liquid-phase microextraction (PI-LPME; enrichment ∼144×). One PI-LPME paper can be directly coupled to a lateral flow immunoassay, for initial screening. In case of a suspect sample, the other PI-LPME paper is transported to a laboratory, where it can be stored at room temperature (recovery >90%, no difference between 1 and 10 days of storage). The PI-LPME paper can then be analyzed with paper spray-(high resolution) mass spectrometry (PS-(HR)MS). Using atropine-d5 as internal standard, the PS-HRMS method could reach detection limits in matrix almost as low as HPLC-HRMS, respectively 1.2–2.7 μg kg−1 and 0.2–1.3 μg kg−1. Furthermore, the accuracy and precision of the PS-HRMS method was comparable to HPLC-HRMS for buckwheat cereals (precision: 8.7%–9.6% vs. 7.6%–10%, accuracy: −4.0%–17% vs. −6.7%–15%) and canola oil (precision: 6.4%–10% vs. 1%–1.8%, accuracy: −12%–7.7% vs. −2.4%–1.9%). Significance: Our paper-based workflow has the potential to aid in the fast and affordable monitoring of atropine. Importantly, the method's suitability is demonstrated for diverse matrices, and it is expected that it can be easily adapted to monitor for other food safety hazards – given the wide applicability of liquid-liquid extractions.