Importance of mobile phase and injection solvent selection during rapid method development and sample analysis in drug discovery bioanalysis illustrated using convenient multiplexed LC-MS/MS

Multiplexed LC-MS/MS was first introduced into the bioanalytical laboratory to increase sample throughput at relatively low cost as multiple LC systems are connected to a single mass spectrometer through a series of switching valves. Traditionally used for staggered parallel analysis, they can also serve as flexible systems for performing independent analyses on each of their channels during method development or sample analysis. Herein, the importance of mobile phase and injection solvent selection for rapid method development and sample analysis in drug discovery bioanalysis, facilitated by the use of a multiplexed LC-MS/MS, is demonstrated. The methods thus developed were then conveniently used on the same multiplexed LC-MS/MS unit. In the first example, methods developed for analytes from two different pre-clinical programs, and each applied to a different set of pharmacokinetic (PK) samples, were carried out together on the same multiplexed system unit using separate chromatographic conditions optimized for each study. The second example presents a multi-component analysis of plasma samples from a single PK study, using separate chromatographic conditions optimized for each analyte. Through these examples, our goal was to demonstrate the broad range of applications and advantages of a multiplexed system in the discovery bioanalytical laboratory.