As one of the paths to identify and develop potential preventatives and treatments for COVID-19, researchers had been testing chloroquine and hydroxychloroquine to seek potential therapeutic benefit against COVID-19, later they were determined to be ineffective based on multiple clinical trials. But the significant increase of new prescriptions required FDA to post information regarding drug shortages of chloroquine and hydroxychloroquine. To prepare for the chloroquine and hydroxychloroquine drug products submitted for approval in the US market and help address the drug shortage, this study aims to implement advanced analytical technologies for the quality evaluation of chloroquine and hydroxychloroquine drug products. This work is part of ongoing efforts to develop an advanced analytical platform to ensure a rapid regulatory response to emerging quality and public health issues. The analysis for chloroquine with its six impurities and hydroxychloroquine with its three impurities were carried out on an UHPLC system coupled with tandem mass spectrometer. The chromatographic separation was achieved on an advanced phenyl column with sub-2 µm core-shell particles. A 10-min gradient elution program was set up to ensure the sufficient resolution while maintaining a high-throughput capability. The tandem mass spectrometer was operated with positive electrospray ionization under the Multiple Ion Monitor mode for all the analytes. Both methods were validated according to the requirements of the USP general chapter &lt;1225&gt; validation for compendial methods. The methods with MRM detection have demonstrated sensitivity, selectivity and appropriate analytical ranges for all the analytes with the potential for high throughput capacity of a 10-min run time. The advanced analytical methods were successfully applied to approved drug products in the US market and to further advance a method development platform for rapid regulatory response.

Implementation of advanced analytical methods for quality evaluation of chloroquine and hydroxychloroquine drug products to address drug shortage issues

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