High-Throughput Detection and Quantitation of Metal Contamination with Acoustic Ejection Mass Spectrometry

Metal-catalyzed reactions are integral to medicinal chemistry, yet residual metal contamination in synthesized compounds poses significant challenges for drug discovery. Residual metal ions in reaction products can interfere with biological assays, leading to false positives and unreliable potency results. Traditional techniques like ICP-MS and XRF, while effective, fail to meet the throughput demands of large-scale synthesis. Here, we present a novel approach using Acoustic Ejection Mass Spectrometry (AEMS) for the high-speed detection and quantitation of metal contaminants. Utilizing EDTA as a chelator, the high-resolution AEMS platform identified with high confidence the ten metals most utilized in medicinal chemistry. The platform's high reproducibility, sensitivity, and wide dynamic range allow for the quantitation of metal ions with lower limit of quantification (LLOQ) in the single-digit ppm level. This novel approach meets the high-throughput requirements of modern synthetic chemistry and compound library assessments, streamlining the identification and elimination of metal contaminants.