Authors: Mauro De Pra, Stephan Meding Thermo Fisher Scientific, Germering, Germany
Keywords: Vanquish Core, ISQ EC, ISQ EM, antibiotics, pharmaceutical analysis, stability studies
Goal
Develop a simple, stability-indicating LC-MS method for erythromycin. Compare the impurity profiles of an erythromycin reference standard with stressed analyte.
Application benefits
• Simple fit-for-purpose method development
• Peak assignment based on m/z
• Sensitive detection of analytes with low UV absorption
Introduction
Forced degradation studies are common during early development of drugs. Typically, LC-UV is the technique of choice to profile drug impurities both prior to and after the stress procedure. At this point, some information on the related impurities may be available, such as a list of intermediate products or side-products based on the known synthesis pathway. During early development, standards of such impurities are usually not available, so identification by LC-UV based on their respective retention times is not possible. The LC-UV method developed for a forced degradation study is usually fit-for-purpose, and the effort required for method development should be reasonable. Since the method is usually not validated, or transferred for validation, it is preferred to use generic methods, possibly slightly modified to accommodate the specificity of the analytical target. The method suitability is normally assessed by injecting the active pharmaceutical ingredient (API). If the API peak is resolved from the rest of the impurities the method is considered suitable. However, after a forced degradation, the impurity profile may be substantially different than that of the API reference sample. Therefore, the purity method may no longer be sufficient to resolve all impurities from the API. In this case the method needs to be adapted to the new impurity profile observed for the stressed samples.