Detection of prohibited drugs in blood samples using spray mass spectrometry on plasma-treated paper

This paper proposes a plasma modification-trichlorosilane impregnation composite process for fabricating paper microfluidic channels, which is applied to paper spray mass spectrometry detection of prohibited drugs in serum samples from health supplement addition. Plasma modification plays a dual core role: precisely constructing hydrophilic microchannels on silane-impregnated filter paper and stripping surface residual impurities and ash to optimize physicochemical properties. The plasma-modified microchannel paper spray ionization system (PM-PSI) significantly reduces sample loss during migration versus conventional paper spray ionization (PSI), thus enhancing the detection signal of target analytes in blood samples. Combined with filter paper's matrix effect mitigation and plasma-induced surface optimization, PM-PSI exhibits better detection efficiency than traditional electrospray ionization (ESI) for direct blood sample analysis. Performance validation with venlafaxine showed that PM-PSI increased the signal intensity by 3-5 times and reduced the relative standard deviation (RSD) by 5-6 times compared with PSI at 50-500 ng/mL, and the signal intensity was 10-30 times higher than that of ESI. Quantitative analysis of four typical prohibited drugs (venlafaxine, reserpine, risperidone, sildenafil) revealed their linear range of 1-1000 ng/mL with a significantly improved coefficient of determination (R²) versus PSI. Moreover, PM-PSI coupled with a domestic miniaturized mass spectrometer successfully detected the parent ions of the four drugs at 300 ng/mL, confirming its suitability for complex sample analysis of miniaturized mass spectrometers and providing a technical solution for rapid on-site testing.