(1006-C) A Rapid Method for Simultaneously Determining an Optimal Buffer and the LLOQ of a Small Molecule, a Peptide and a Protein Using a Liquid Handler and an Acoustic Ejection-Enabled QTOF Mass Spectrometer
Tuesday, February 6, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Identifying buffers that yield optimal sensitivity is critical when analyzing compounds, but it can be time-consuming. To make this task more efficient, a rapid method for buffer selection was developed by leveraging automated liquid handling and a prototype acoustic ejection QTOF mass spectrometer. With this approach, the user loads a stock standard of the analyte of interest onto a Beckman Coulter Biomek i7 liquid handler and then executes the protocol. The protocol initially dilutes the stock in 8 different buffers and then further serially dilutes the analyte at 11 different concentrations for each of the 8 buffers. In the study described here, we observed the behavior of dextromethorphan, thyroglobulin peptide VIFDANAPVAVR and ubiquitin (a small molecule, a peptide and a protein, respectively) in each of the 8 different buffer environments. After the dilutions were prepared, 70 nL of each sample was acoustically ejected—a at a rate of 5 seconds per sample—into an open port interface for capture, dilution, and transfer of diluted sample to the electrospray ionization source of a SCIEX ZenoTOF 7600 system using MRMHR and SWATH data-independent acquisition (DIA). Prototype post-analytical analysis allows the user to determine the buffer in which the analyte showed the most sensitivity, while simultaneously determining the lower limit of quantitation (LLOQ) of the analytes in each of the different buffers. This prototype system prepared and analyzed 88 samples in under 20 minutes and provided users with the ability to rapidly select and optimize analytical methods.