Development of a Captiva EMR-lipid clean-up and LC-MS/MS methodology for detecting H2 receptor antagonists in functional foods and food-medicine homology materials

• New method combines CEL-SPE with LC-MS/MS to detect H2RAs in FFs and FMHs. • Captiva EMR-Lipid SPE removes interferences, enhancing sensitivity and accuracy. • Optimized conditions yield high precision, recovery rates, and low detection limits. • It offers effective means to ensure product safety and consumer health. The inappropriate use of H2 receptor antagonists (H2RAs) in functional foods (FFs) and food-medicine homology materials (FMHs) designed to enhance gastrointestinal function (IGF) presents health risks due to potential adverse effects. In this study, an analytical method that integrates Captiva EMR-Lipid (CEL) solid-phase extraction (SPE) with liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed for the detection of H2RAs (nizatidine, famotidine, cimetidine, ranitidine, and lafutidine) in these products. Through the optimization of CEL-SPE parameters, such as using 200 mg of sorbent and eluting with ACN/water (80/20, v/v), the recovery rates of H2RAs in IGF-FF and IGF-FMH ranged from 87.4% to 94.6% and 90.2% to 97.1%, respectively. The assessment of matrix effects revealed that the five H2RAs exhibit matrix suppression, necessitating the construction of matrix-matched standard curves with correlation coefficients (r 2 ) exceeding 0.9991. The detection limits ranged from 0.4 to 0.8 μg·kg −1 and the quantification limits ranged from 1.3 to 2.7 μg·kg −1 , with recovery rates spanning from 85.4% to 97.1% and relative standard deviations ≤ 15%. The successful development of this technique not only helps safeguard consumer health but also provides scientific basis and technical support for market supervision, thereby preventing and addressing food safety risks.