The direct and online determination of antibiotics from complex matrix via paper spray ionization with mask materials

Advances in mass spectrometry for antibiotics determination are highly sought, with ambient ionization mass spectrometry (AIMS) providing a promising pathway for rapid and straightforward analysis of complex samples. However, effectively separating antibiotics in complex matrix using AIMS remains challenging due to high salt concentrations and complex substrate. Here, we introduce a technique—paper electrospray ionization with mask materials (PSI–M)—for the separation of antibiotics in complex matrix through online adsorption and desorption. The PSI–M employs a triangular mask for loading the liquid analyte, quantitative analysis of clarithromycin was performed in bovine whole blood and simulated seawater. Under optimized conditions, the proposed PSI–M has a low limit of detection (0.4 ng mL⁻¹ in bovine whole blood and 1.2 ng mL⁻¹ in simulated seawater), a wide linear dynamic range (1–10,000 ng mL⁻¹ in bovine whole blood and 1–1000 ng mL⁻¹ in simulated seawater), and has good selectivity, repeatability and stability. Compared to conventional PSI, PSI–M significantly improves spray stability, extends analysis duration, and generates substantially higher signal intensity during substance analysis, thereby underscoring its potential for applications. Moreover, PSI–M enables the separation and rapid, sensitive analysis of complex matrix, encompassing bovine whole blood, artificial urine, simulated seawater, and water samples with varying salinity. This advancement offers a viable solution for the rapid online separation and determination of antibiotics in complex matrix.