Good Manufacturing Practices (GMPs) are required from the building block starting material (SM) and intermediate forward in the manufacture of pharmaceutical drug substance API. A novel synthesis of the SM/intermediate may contain various related impurities that could be carried over at a level above the ICH Q3A identification threshold and are considered to have an impact on the impurity profile of the API. Characterization and quantitation of these early building block compounds provide important data for drug safety specifications and are required for regulatory filing.<br/>Analytical methodology should be capable of detecting a wide range of possible impurities based on different physical and chemical separation and detection principles with appropriate acceptance criteria. However, SM/intermediate compounds often lack chromophores to be detected by UV and are highly polar and difficult to be retained in conventional reverse phase HPLC. In addition, the properties of these building block molecules render them too volatile for detection under charged aerosol detector (CAD). Some starting materials used for synthesis may be reactive and temperature sensitive, therefore not suitable for GC analysis.<br/> <br/>This work present the development of purity assay for a series of SM/intermediate compounds possessing no UV response and are too volatile for UV and CAD detection. We experimented with various ion-paring reagents such as TFA and HFBA to demonstrate that salt formation through ion-pairing modifiers can significantly reduce volatility to achieve better detection of the compound by CAD. Selection of ion-pairing agent is important to help gain the maximum CAD response and at the same time yielding optimum chromatographic separation.<br/>

Purity analysis of volatile/reactive building block chemicals without UV chromophore by HPLC-charged aerosol detection

256th National Meeting (2018)

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