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The use of the hyphenated LC-MS/MS technique for the characterisation of impurity profile of Quetiapine during drug development

Elżbieta U. Stolarczyk ,  Andrzej Kutner 

Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


     As a part of an integrated quality concept for impurities during drug development, the multidimensional evaluation of impurity profiles by LC-MS/MS coupling is presented using Quetiapine active pharmaceutical ingredient (API) as an example. Although the LC-UV is commonly employed for the impurities and degradant compounds  determination, the LC-MS/MS technique is proposed in this work as a viable modern alternative for the characterization of these compounds. The case study outlines the use of LC-MS/MS technique in developing methods for the separation and identification which enable the determination of both process and degradation impurities.

     The developed methods of the impurity-profile determination allow monitoring impurity profile changes, resulting from both planned and unplanned changes in the synthesis or the API storage. The developed methods also enable the identity confirmation of the studied API, structure elucidation and identification of the impurities from the synthesis route (isolated, synthetised, and those which were not successfully isolated or synthetised), as well as the impurities resulting from the degradation of the studied pharmaceutical substance which were not obtained as standards. The mass spectra, fragmentation spectra and chromatographic information about the order of elution were all used to identify the impurities. The proposed structures of process impurity were additionally confirmed by analysing the route of synthesis of the studied pharmaceutical substance. On the basis of the proposed structures of API degradation impurities their formation mechanisms were presented.


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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Elżbieta U. Stolarczyk
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-11 16:01
Revised:   2010-04-23 09:50