Modify on the fly: triple quad to high resolution in support of a dermal clinical study requiring an ultra low LLOQ

Background: FTIH studies can be challenging due to the varying dosing regimens and rapid data delivery. Chemists are asked to provide ultra-low limits of quantitation to provide an understanding of patient efficacy and safety in order to progress drug development. In a recent dermal study it became necessary to reduce the LLOQ of a small molecule drug from 50 to 1 pg/ml due to reductions in the dose and surface area of drug application. Methodology: The 50-fold increase in assay sensitivity necessitated the use of a high-resolution mass spectrometer (LC–HRMS) to separate matrix interferences observed when using a unit resolution...