Structure determination of unknown impurities

Analytics and evaluation

At SGS we distinguish between the following two types of impurities:

1. Structure determination of unknown Active Pharmaceutical Ingredient (API) impurities
   These impurities are in particular by-products of synthesis and/or degradation products of the active pharmaceutical ingredient.
2. Unknown impurities in pharmaceuticals
   Impurities occur not only in the early stages of drug development, but also, for example, during stability determination and formulation changes. There are numerous causes for this, e.g. other synthesis routes, interactions with excipients and/or packaging material (leachables), polymorphic transformations.

If a by-product or degradation product exceeds the specified limit, the structure of the impurity must be determined. Since the impurities are usually present only in small amounts, it is necessary to use special analytical techniques (e.g., (U)HPLC-QToF-MS(MS)) to determine the structure. Often, the impurities are detected during HPLC-UV analysis of the active ingredient or drug product. In most cases, it is not possible to obtain mass spectrometric data directly using these HPLC-UV methods. 

At the SGS Analytics site in Aachen, Germany, we therefore offer a solution using (2D)-(U)HPLC-DAD-QToF-MS(MS) with Multiple Heartcut technology. Here, the original HPLC method can be used in the first chromatographic dimension. With Multiple Heartcut technology, the impurity of interest is isolated and analyzed by mass spectrometry or tandem mass spectrometry in the second chromatographic dimension.

In some cases, structure determination is followed by specific synthesis of the impurity or semi-preparative isolation of the impurity and its qualification as a standard.