Acoustic ejection mass spectrometry: fundamentals and applications in high-throughput drug discovery

Introduction Acoustic ejection mass spectrometry (AEMS) is an electrospray ionization-mass spectrometry (ESI-MS) based analytical platform that provides high analytical throughput and data quality. It has been applied in numerous drug discovery workflows, such as high-throughput screening (HTS), absorption, distribution, metabolism, and excretion (ADME) profiling, pharmacokinetics (PK) analysis, compound quality control (QC), and the high throughput readout of medical chemistry samples. Areas covered This paper introduces the working principle of AEMS technology. The analytical performance, system tuning and method development workflows, and representative applications on high-throughput drug discovery assays are introduced. Expert opinion The fast sample readout speed, high reproducibility, wide compound coverage, minimum carryover, and the tolerance to complex sample matrices of AEMS have demonstrated its advantages over other technologies in this field, with broad applicability to a diverse range of drug discovery workflows. However, the current platform still has challenges for some assays due to having less sensitivity compared with liquid chromatography-mass spectrometry (LC-MS), and the lack of chromatographic separation for isomeric interferences. Despite the remaining hurdles, AEMS is becoming an attractive high-throughput analytical platform in drug discovery. Additional system developments would enable its further adoption in the future.