Identification andMitigation of Pyrolysis Productsin Laser-Cut Paper for Paper Spray Mass Spectrometry

Paper spray mass spectrometry (PS-MS) often employs laser cutting to prepare paper substrates, potentially inducing localized thermal decomposition of the cellulose backbone. This work investigates how cellulose pyrolysis products and inherent background molecules within the paper affect PS-MS signal quality and evaluates paper pretreatment methods to enhance performance. Comparative analyses of laser-cut and razor-cut paper using mass spectrometry and ultraviolet–visible spectroscopy (UV–vis) showed significant differences. Laser-cut paper exhibited elevated MS blank signals and higher absorbance in the 200–400 nm UV region, indicating increased chemical abundance and complexity. Gas chromatography–mass spectrometry (GC-MS) identified over 20 residual compounds on laser-cut paper absent in razor-cut samples, half of which were identified as known cellulose pyrolysis products. Washing the paper substrates with methanol, water, or dilute nitric acid significantly reduced both pyrolysis products and background molecules, with water showing the most improvement. Analyses of morphine, fentanyl, methamphetamine, voriconazole, and fluconazole showed no reduction in the signal after washing, with fentanyl and methamphetamine exhibiting a significantly increased MS signal, regardless of the cutting method. This work reveals that while pyrolysis products from laser cutting contribute to increased chemical noise, inherent background molecules in the paper also play a significant role. A simple water wash mitigates both issues, potentially improving the overall PS-MS performance for a range of analytes.