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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Evaluation of a UPLC-MS method using 18O-labelled water for the identification of hydrolytic degradants of drug substances

Kjellberg, Viktor January 2015 (has links)
In this master’s thesis the hydrolytic degradation in 18O-water solutions of six drug substances has been studied. The aim was to develop a mass spectrometric method for easier identification of degradants, since hydrolysis in 18O-water will generate degradants with higher mass compared with hydrolysis in regular water. The degradation was carried out in both acidic and basic conditions. About 10 % degradation was aimed for in the study and the storage time and conditions were adjusted to accommodate that. The samples were then analyzed with UPLC-MS. Separation was achieved on either an Acquity BEH C18 or HSS T3, 100 x 2.1 mm, 1.7 μm column. The mobile phases consisted of water and acetonitrile with the addition of 0.1 % formic acid. Structures for the detected degradants were proposed based on the molecular ion data from the regular and 18O-experiments. Most of these degradants have previously been reported. Structures for some previously unreported degradants are also proposed. These structures should need to be confirmed with future studies. The usefulness of the 18O-method has been evaluated and it was concluded that it is valuable to use as a complement to the generic hydrolytic experiment. In this study, the extra information gained from the 18O-experiment was used to confirm a number of proposed structures. It was also crucial in the rejection of two proposed structures for degradants of duloxetine. The method is most useful when confirming water involvement in reactions, for example in drug degradation. It is also a good alternative for obtaining structural information if the laboratory does not own a high-resolution MS.

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