Challenges in development of robust analytical methods for the quantitation of low molecular weight compounds by LC-MS/MS

Method development can be considered one of the most challenging task in a Bioanalytical laboratory. When working with LC-MS/MS and low molecular weight drugs, low degree of ionization, poor fragmentation, higher presence of isobaric compounds or analyte loss due to their high volatility can get in the way of a successful method development.

In the work we presented during the 7th Young Scientist Symposium, we aim to provide ideas and strategies to help tackle and solve these problems, based on real issues encountered during method development.

The advice given in the poster when working with low mass compounds focuses on three main points:
• Evaluate alternative ionization sources in order to potentially reduce background noise and increase overall sensitivity.
• Carefully evaluate and investigate the evaporation step in order to reduce cross-contamination, even avoid it altogether when possible.
• Higher presence of endogenous isobaric compounds, that can have the same MRM transition, means that the chromatographic separation has to be extensively optimized. Good chromatographic separation of all isobaric compounds is paramount to avoid erroneous conclusions.

You may find the poster below for your ready reference:


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