Development of analytical methods for determination of drugs, used against tropical diseases, in biological fluids

Document identifier: oai:dalea.du.se:1795
Publication year: 2006
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Abstract:

The overall aim of this thesis was to develop analytical methods for determination of drugs, used against tropical diseases, in biological fluids. For the treatment of malaria, piperaquine (PQ) is used in combination with another antimalarial. Human African trypanosomiasis is treated with eflornithine (DFMO), a chiral drug administered as a racemic mixture. A method for determination of PQ in capillary blood applied and dried onto sampling paper has been developed and validated. This method uses perchloric acid and acetonitrile to extract PQ from the biological matrix and sampling paper. The liquid phase is then loaded onto a strong cation-exchange solid-phase extraction column. PQ and the IS are separated on a Chromolith Performance column at high flow rate, allowing fast chromatography, and detected with UV absorbance detection. Capillary blood sampling onto sampling paper facilitates clinical studies performed in the field, eliminates need of venipuncture, simplify storage as well as transportation and makes handling samples safer for laboratory personnel. A method for determination of underivatized DFMO enantiomers in plasma has been developed and validated. Proteins are percipitated with trichloro acetic acid and the liquid phase is loaded onto a strong cation-exhange solid-phase extraction column. D-DFMO and L-DFMO and the IS are separated on a Chirobiotic TAG column with a chiral stationary phase. Detection is performed using evaporative light-scattering detection. This method allows study of behavior of individual enantiomers in humans. There is an indication that D-DFMO and L-DFMO differ and this needs to be investigated further. Therefore, a chiral method of determination is of value. This method has also been evaluated for determination of DFMO enantiomers in cerebrospinal-fluid.

Authors

Mikaela Malm

Högskolan Dalarna; Kemiteknik
Other publications >>

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    header: 
        identifier: oai:dalea.du.se:1795
        datestamp: 2021-04-15T12:04:31Z
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                version: 3.7
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                recordContentSource: du
                recordCreationDate: 2006-02-27
            identifier: http://urn.kb.se/resolve?urn=urn:nbn:se:du-1795
            titleInfo: 
                @attributes: 
                    lang: eng
                title: Development of analytical methods for determination of drugs used against tropical diseases in biological fluids
            abstract: 
The overall aim of this thesis was to develop analytical methods for determination of drugs used against tropical diseases in biological fluids. For the treatment of malaria piperaquine (PQ) is used in combination with another antimalarial. Human African trypanosomiasis is treated with eflornithine (DFMO) a chiral drug administered as a racemic mixture.\nA method for determination of PQ in capillary blood applied and dried onto sampling paper has been developed and validated. This method uses perchloric acid and acetonitrile to extract PQ from the biological matrix and sampling paper. The liquid phase is then loaded onto a strong cation-exchange solid-phase extraction column. PQ and the IS are separated on a Chromolith Performance column at high flow rate allowing fast chromatography and detected with UV absorbance detection. Capillary blood sampling onto sampling paper facilitates clinical studies performed in the field eliminates need of venipuncture simplify storage as well as transportation and makes handling samples safer for laboratory personnel.\nA method for determination of underivatized DFMO enantiomers in plasma has been developed and validated. Proteins are percipitated with trichloro acetic acid and the liquid phase is loaded onto a strong cation-exhange solid-phase extraction column. D-DFMO and L-DFMO and the IS are separated on a Chirobiotic TAG column with a chiral stationary phase. Detection is performed using evaporative light-scattering detection. This method allows study of behavior of individual enantiomers in humans. There is an indication that D-DFMO and L-DFMO differ and this needs to be investigated further. Therefore a chiral method of determination is of value. This method has also been evaluated for determination of DFMO enantiomers in cerebrospinal-fluid.

            language: 
                languageTerm: eng
            genre: 
                publication/licentiate-thesis
                vet
            note: 
                Published
                1
            name: 
                @attributes: 
                    type: personal
                    authority: du
                namePart: 
                    Malm
                    Mikaela
                role: 
                    roleTerm: aut
                affiliation: 
                    Högskolan Dalarna
                    Kemiteknik
                nameIdentifier: mml
            originInfo: 
                dateIssued: 2006
                publisher: Uppsala Universitet Department of Chemistry Analytical Chemistry
                place: 
                    placeTerm: Uppsala 
            physicalDescription: 
                form: print
            typeOfResource: text