A novel 'peak parking' strategy for ultra-performance liquid chromatography/tandem mass spectrometric detection for enhanced performance of bioanalytical assays.

Sensitive and high-throughput bioanalytical assays are of vital importance to drug discovery and development. Ultra-performance liquid chromatography (UPLC), utilizing sub-2-microm particles, greatly increases the separation throughput and efficiency, resulting in LC peaks as narrow as or less than 1 s (full width at half maxima, FWHM). This, however, could pose practical challenges for bioanalytical applications using quadrupole mass spectrometry (MS) to acquire sufficient data points to ensure accurate and reliable quantitation. Here, we present a novel 'peak parking' strategy to reduce the flow rate during UPLC peak elution, therefore extending the useful MS acquisition window. The high-throughput advantage of UPLC is maintained since no significant increase of the overall UPLC run time is needed. This strategy was demonstrated in an assay development for lansoprazole, a gastric proton-pump inhibitor, in human plasma employing liquid-liquid extraction. The method was validated from 50.0 to 50,000 pg/mL.