Purification Services

The Purification/Reclamation Services team at FSSI is dedicated to providing high quality, high throughput preparative scale LC-MS purifications as well as preparation of screening plates from purified samples.  The result is a dramatic reduction in the time from synthesis to screening.

Many compounds contain impurities or will show some amount of decomposition over time due to atmospheric exposure or general instability.  While the cost of replacing these compounds by re-synthesis or purchasing can be prohibitive, reclaiming the pure compounds through purification techniques and/or chemical transformations can offer tremendous cost savings.  In addition, the purified compound can often be obtained in a much shorter amount of time than re-synthesis would require.

FSSI offers cost effective compound purification and reclamation services using a number of purification techniques.  Typically 80 – 90 % of the desired compound present in the sample can be recovered in 90 - 97% purity using these methods.  In addition to the cost and time savings, this service offers significant environmental benefits as the multiple waste streams generated by compound synthesis are virtually eliminated.

As part of this service, FSSI provides:

  • Purification method recommendation.
  • Use of multiple techniques in sequence where required.
  • Analytical characterization (NMR, LCMS, GCMS) both before and after the compound is purified.
  • Characterization of major impurities  (NMR, LCMS, GCMS)
  • Structural determination of major impurities in select cases
    • Minor changes determined by NMR and LCMS/GCMS
    • Larger differences may be determined through X-ray diffraction where desired (and where quality crystals can be obtained)


Methods typically employed include:
Chromatography

  • Standard normal phase chromatography on silica gel or alumina using either glass columns or Biotage equipment.  Useful for most compounds that do not have highly polar groups.
  • Typical scale:  1 – 100 g (larger scale available)
  • Typical time required:  1 day


Trituration

  • Separation of compound from impurities through careful solvent selection that allows impurities to dissolve while the desired compound stays behind or allows pure compound to dissolve while impurities remain behind.  Useful for solid compounds where impurities have a significantly different solubility profile than the desired compound.
  • Typical scale:  5 – 1000 g
  • Typical time required:  1 day


Crystallization

  • Separation of compound from impurities through careful solvent selection that allows pure compound to crystallize from solution while impurities remain dissolved.  Useful for solid compounds where impurities’ solubility profile is too similar to that of the desired material to separate by trituration.
  • Typical scale:  5 – 1000 g
  • Typical time required:  2 days


Distillation

  • Separation of compounds based on boiling point.  We have the ability to perform most distillation techniques including use of short path distillation head, Vigreux columns, bulb-to-bulb distillation at atmospheric pressure to high vacuum.  Useful for thermally stable compounds where impurities have a boiling point sufficiently different than the desired compound.  In general GCMS will be performed prior to the distillation to get an idea of boiling point and stability, and another purification technique may be used to remove impurities that could cause tar formation (often silica plug and/or activated charcoal treatment)
  • Typical scale:  5 – 1000 g
  • Typical time required:  2 days


Prep-LCMS

  • Reverse phase chromatography on C8 or C18 preparative scale HPLC columns with mass triggered fraction collection .  Two instruments are currently available with a capacity of 30 – 100 injections per day.  The best method for running each compound is determined using an analytical LCMS run prior to the preparative scale run.
  • Typical scale:  5 mg – 1  g (typically 120 mg per injection)
  • Commonly used for:  HTS compounds, compound libraries
  • Typical time required:  2 days (This is the time for a single compound.   Significant time savings per compound occur when multiple compounds are provided for prep-LCMS at the same time)


Prep-TLC

  • Normal phase preparative scale TLC plates.  Can be useful for parallel separation of compounds typically run by prep-LCMS where purity requirements are less stringent.  Usually requires good chromophores in the desired product and impurities (except where sacrificing 5 – 10% of the compound is acceptable)
  • Typical scale:  5 mg – 1  g (typically 50 – 500  mg per plate)
  • Typical time required:  2 days

 

Materials Management and More