“…Then, the porous solid-substrate-based ambient ionization techniques, such as paper spray ionization, , wooden-tip electrospray ionization, − carbon fiber spray ionization, and others, − had demonstrated their potential for rapid, direct, and in situ analysis of drugs in urine, blood, tissue, and tablets. − The characteristic ions were produced directly from analytes present in trace powders, biological fluids, and viscous samples on the solid substrate by adding a proper solvent and applying a high voltage to cause desorption and ionization. To further improve the sensitivity and selectivity of these methods, surface-coated paper spray ionization techniques were developed to analyze the therapeutic drugs in DBS. , Moreover, the thermal-desorption-based ionization methods, such as atmospheric pressure chemical ionization (APCI), DART, and thermal desorption electrospray ionization, − suffered less from the matrix effects due to the two steps of desorption and ionization in time and space. Thus, the thermal-desorption-based direct ionization techniques were very important for analysis of biological samples, especially for illicit drug analysis in urine or blood.…”