Portable mass spectrometers have played an important role in the rapid field detection of drugs
however, interference from matrix components, such as salts, solvents, and other metabolites, often leads to high rates of false positives and false negatives, making it challenging to meet the requirements for rapid field detection. To mitigate these challenges, a solvent-assisted thermal desorption ionization source has been developed, which enables rapid screening, improved accuracy and quantitative MS analysis. This ionization source is designed to allow the introduction of sample solution into the thermal desorption chamber with coaxial solvent and gas flows. The sample is introduced into a closed high-temperature thermal desorption chamber by the coaxial gas flow, where it is rapidly vaporized, enabling a concentrated ionization and avoiding chemical interferences from the environment. The use of both a solvent flow and a guiding gas flow in the new ion source design effectively reduces the sample deposition on the inner surface of the glass liner in the thermal desorption chamber and minimize cross contamination and the interferences from salts in the sample, a significant 1.8-5 fold enhancement in the signal intensity of the drug was observed, and accommodates a large sample volume injection for a significantly increased sensitivity, repeatability, and accuracy of MS detection. By integrating this novel solvent-assisted thermal desorption ionization source with a portable mass spectrometer and employing a selected ion monitoring (SIM) mode, the linear dynamic ranges of detection for ketamine, cocaine, and morphine in the hair matrix have shown to be 1-20 ng/mg, with R