2,2,2‐Trifluoro‐1‐(5‐Bromo‐2‐Nitrophenyl)‐Ethanol as a Reactive Matrix for Laser Desorption/Ionization Mass Spectrometry

Matrix‐assisted laser desorption/ionization (MALDI) has been widely used in mass spectrometry (MS) detection of a great variety of biomolecules in complex biological systems but suffers from several constraints including poor ionization properties, signal suppression, and matrix‐related background interference in the low mass range. Herein, we demonstrate a reactive MALDI matrix, 2,2,2‐trifluoro‐1‐(5‐bromo‐2‐nitrophenyl)‐ethanol (TFBNPE), to overcome these limitations. TFBNPE combines an aromatic ring for ultraviolet laser absorption, a side chain for primary amine group reaction, and a bromine atom for isotopic identification. The derivatization process using TFBNPE enhances analyte ionization and introduces characteristic isotopic patterns due to the bromine atom, facilitating unambiguous identification of primary amine‐containing biomolecules. This approach effectively ameliorates isobaric interferences in the low mass range, significantly improving detection sensitivity and reliability. Our findings demonstrate the great potential of TFBNPE for sensitive and selective MALDI‐MS analysis of diverse biomolecules.