Project Goal

To assess the advantages of moving from ligand binding assays (LBA) to microflow LC-MS/MS for large molecule bioanalysis and how the source design affects performance gains.

The Challenges

• Inadequate sensitivity and selectivity for some bioanalytical assays using LBA or conventional flow LC-MS/MS
• Any new equipment and methodologies must be rugged and reliable, and require minimal optimization
• Any changes to established equipment and methodologies must require minimal new training of lab personnel

The Solution

• Microflow LC-MS/MS using the Optiflow® Ion Source with our SCIEX triple quadrupole instruments. Column directly connects to source

The Outcomes

• Large gains in peak area and peak height with microflow LC-MS/ MS and Optiflow Source for large and small molecule bioanalysis, equating to major improvements in S/N (4-20x) and lower LLOQ
• Direct connection port for LC column minimizes dead volume resulting in less band broadening, less tailing, and more narrow peaks
• Source requires minimal to no optimization
• Source requires less than 10 minutes of training
• Have now analyzed many samples to support both clinical and pre-clinical large and small molecule studies by microflow LC-MS/MS using the Optiflow Source including some challenging programs that had selectivity and sensitivity issues that were solved with this workflow