Building a Bridge Between Ambient MS and LC-MS by Non-Exhaustive Microdesorption.

Ambient mass spectrometry (AMS) offers rapid screening but faces challenges in analyzing complex samples due to high matrix effects. The absence of a separation step can also lead to false positives due to the isomers or isobars. In this study, a sequential analysis strategy which combines ambient MS and LC-MS based on the non-exhaustive microdesorption in solid-phase microextraction (SPME) was developed for the first time. By combining coated blade spray (CBS)-MS with LC-MS, in the first step, a few microliters of solvent were used for non-exhaustive desorption with high enrichment factor for rapid screening by CBS-MS. For the suspicious samples, the remaining analytes on the SPME coating undergo exhaustive desorption, then followed by LC-MS confirmation. The matrix-compatible coating used in the SPME device significantly reduces matrix effects while enhancing sensitivity through analyte enrichment. This method is environmentally friendly, utilizing only a few microliters of organic solvents for screening. The approach was rigorously validated, both theoretically and experimentally, and successfully applied to anti-doping testing, enabling detection of 53 prohibited substances in urine samples by integrating CBS-MS with LC-MS.