Pharmaceutical Impurities and Degradants

Impurities and Degradants can be present in raw materials, arise during the manufacturing process, be generated during storage or evolve following sample incorporation into a closed container system.

The key to identifying impurities and degradants is having the right equipment, expertise and experience to generate insightful data and interpret this data in a practical way.


 

Impurities and degradants identification techniques

Separation techniques such as HPLC and GC, when hyphenated to mass spectrometry, provide analytical platforms which are capable of generating the most defensible data for the isolation and investigation of unknowns.

Following chromatographic separation of impurities and degradants, with any necessary peak purity determination, the resultant mass spectrum of an unknown may be searched and compared against established libraries or user-contributed databases to facilitate identification.

Alternatively, first principles ab. initio. mass spectral interpretation in conjunction with a proposed structure or known intermediate may elicit a proposed structure. Further structure corroboration may be provided by accurate mass determination which will yield empirical formulae proposals of the intact unknown precursor and its resultant product ions.

Our analytical laboratory has the wide variety of instrumentation required to identify unknowns, impurities and degradants. In addition to analysis alongside standards, accurate mass and MS-MS techniques provide complementary data. These techniques can also be used to complement data generated in the client’s own QC laboratory.

ICH guideline Q1A(R2) defines the stability data package for a new drug substance or drug product that is sufficient for a registration application within the three regions of the EC, Japan and the United States.

The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity and light, and to establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions.

Through our trusted out-sourcing partners we can provide environmental conditions as defined in the ICH guidelines with subsequent routine testing or the development and validation of stability indicating methods carried out at Hall Analytical. Storage stability trials to current ICH guidelines:

  • 25ºC/60% RH, 30ºC/65% RH, 40ºC/75% RH and more temperature and humidity cabinets
  • Storage at -80, -20, -10, 0, 5, 10, 25, 40, 54ºC
  • Continuous Ice-Spy monitoring and alerts
  • Photo-stability testing
  • Post-marketing stability and shelf life studies