Identification


Elucidating “Unknown Substances”

Chemical structure elucidation of unknown peaks: This might be metabolite profiling or identifying your impurities or degradation products (= impurities of drug product). Thorough knowledge about your own product (beyond your API itself) is increasingly demanded by the authorities and guidelines: Impurities, degradation products, side and byproducts (see Impurities & Degradation Products).


  • Metabolite Profiling
  • Impurities
  • Degradation Products

  • Possibly the most important thing we have learned about metabolism over the years is that metabolic behavior should be understood sooner rather than later in a development project.

    Nowadays metabolite profiling shouldn´t be a big deal: For a skilled expert it´s a matter of days rather than weeks or months. Our abilities are derived from long-term experience and state-of-the-art instruments.

    Example Metabolite Profile:

  • Impurities in New Drug Substances:
    “Any component of the new drug substance that is not the chemical entity defined as the new drug substance.”
    (Source definition: ICH guidance for Industry-Q3A Impurities in New Drug Substances, June 2008)

     

    Various impurities are defined:

    Enantiomeric Impurity:
    A compound with the same molecular formula as the drug substance that differs in the spatial arrangement of atoms within the molecule and is a non-superimposable mirror image.

    See our services in regards to enantiomeric separation.

    Extraneous Contaminant:
    An impurity arising from any source extraneous to the manufacturing process.

    Intermediate:
    A material produced during steps of the synthesis of a new drug substance that undergoes further chemical transformation before it becomes a new drug substance.

    Thresholds given in the ICH guideline:

    Maximum Daily Dose1 Reporting Thresholds 2,3 Identification Threshold3 Qualification Threshold3
    ≤ 2g/day 0.05% 0.10% or 1.0 mg per day intake
    (whichever is lower)    		 0.15% or 1.0 mg per day intake
    (whichever is lower)
    > 2g/day 0.03% 0.05% 0.05%

     

     

     

     

    1 The amount of drug substance administered per day
    2 Higher reporting thresholds should be scientifically justified
    3 Lower thresholds can be appropriate if the impurity is unusually toxic

     

    Contact us for elucidation of impurities.

  • Impurities in New Drug Products “

    “An impurity resulting from a chemical change in the drug substance brought about during manufacture and/or storage of the new drug product by the effect of, for example, light, temperature, pH, water, or by reaction with an excipient and/or the immediate container closure system.”
    (Source definition: ICH guidance for Industry-Q3A Impurities in New Drug Products, July 2006)

    Thresholds given in the ICH guideline: