Optimized Reactive Metabolite Trapping Assays: Increased Quality and Throughput Using High Resolution Mass Spectrometer, Stable Isotopes and Data Mining Software

摘要

1. Considering the cost saving of stable labeled GSH, a 3:1 ratio with three fold less labeled GSH is recommended, which will not sacrifice isotopic ratio accuracy and numbers of neutral loss, but with less of 25% GSH conjugates found comparing with 1:1 ratio. 2. A 1:1 ratio is recommended for KCN and methoxylamine trapping. 3. We were able to run 48 samples per week if necessary using this approach without loss of data quality. 4. With this report format, we are able to upload data to central location, which helps us or chemists to compare with TDI data and figure out SAR. 5. Eventually to help project team to find the best scaffold with less reactive metabolites and low TDI.