During the drug development process, unknowns often arise from impurities and degradation products that can be formed during the manufacturing process and/or storage of the new drug. Current United States Food and Drug Administration (USFDA) regulatory guidance requires that studies be conducted to identify the impurities present in a new drug substance (if they are at a level greater than the identification threshold) and to characterize their structure (USFDA, Guidance for Industry, Q3A Impurities in New Drug Substances).
Impurity Characterization Studies
MicroConstants characterizes and potentially identifies impurities and degradation products present in your API to support drug discovery programs. This information can be used to help with non-GLP animal studies and to guide CMC analysis of API used in GLP studies.
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Method Development & Analysis of Impurities
MicroConstants will either develop a suitable method, or adapt an existing method for the impurity characterization study. If an existing method is provided, attempts will be made to match relative retention times of the compound and/or the noted impurities. If necessary, alternative conditions to optimize separation of the impurity can also be developed.
During the study, we will dissolve the API in the appropriate solvent at the required concentration (either provided by the sponsor, or determined during development) and use the pure compound to determine spectrometer conditions. Samples will then be injected in both positive and negative modes (when applicable) per the method and full scan high resolution mass data and diode-array UV data will be collected for all impurities.
Chromatograms, retention times, accurate masses, and product ion spectra of the known and unknown peaks will be collected during the study. Attempts will then be made to identify the unknown peaks and peaks of interest using available software tools including Metabolynx, Mass Fragmenter, and isotope modeling.
The results from impurity characterization studies can be presented as a formal report suitable for regulatory submissions, or as an informal report (i.e. raw data tables in Excel format).