Automated Sampling For Improved Impurity Profiling - METTLER TOLEDO

White Paper

Automated Sampling For Improved Impurity Profiling

Unattended, Representative Sampling of a Wide Range of Chemical Reactions

Although sampling chemical reactions for offline analysis is standard, it is not always precise and reproducible.  Delays in quenching can lead to variable results and inaccurate analytical information. In Pfizer's synthetic chemistry and process development laboratories, these challenges have been eliminated with an automated and robust inline method of taking representative samples from reactions, even under difficult conditions.  Unattended sampling was applied in long-term stability studies over several days and to reactions which require immediate quench-in-place operation at reaction temperatures.

This white paper reviews four case studies where unattended, automated chemical reaction sampling was successfully used by Pfizer researchers for:

1. Removing Barriers for Impurity and Kinetics Profiling in an Ullman Reaction
2. Improving Confidence by Measuring the Effect of Process Parameters on an Imidazolide Reaction
3. Extending Productivity with Endpoint Detection in a C-H Reaction
4. Ensuring Successful Scale-up of an Amination Reaction

Reactions that Pfizer successfully sampled include:

  • Thick Slurries
  • Dark Mixtures With Inorganic Salts Present
  • Tri-Phasic Mixtures
  • Oxygen-Sensitive Reactions

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