Simultaneous quantification of the highly lipophilic atovaquone and the hydrophilic strong basic proguanil and its metabolites, using a new mixed-mode SPE approach and Steep-Gradient LC

Document identifier: oai:dalea.du.se:1203
Access full text here:10.1093/chromsci/43.5.259
Keyword: Engineering and Technology, Chemical Engineering, Teknik och teknologier, Kemiteknik
Publication year: 2005
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Abstract:

A bioanalytical method is described for the simultaneous quantitative analysis of the highly lipophilic atovaquone and the strong basic proguanil with metabolites in plasma. The drugs are extracted from protein precipitated plasma samples on a novel mixed-mode solid-phase extraction (SPE) column containing carboxypropyl and octyl silica as functional groups. The analytes are further separated and quantitated using a steep-gradient liquid chromatograhic method on a Zorbax SB-CN column with UV detection at 245 nm. Two different internal standards (IS) are used in the method to compensate for both types of analytes. A structurally similar IS to atovaquone is added with acetonitrile to precipitate proteins from plasma. A structurally similar IS to proguanil and its metabolites is added with phosphate buffer before samples are loaded onto the SPE columns. A single elution step is sufficient to elute all analytes. The method is validated according to published guidelines and shows excellent performance. The within-day precisions, expressed as relative standard deviation, are lower than 5% for all analytes at three tested concentrations within the calibration range. The between-day precisions are lower than 13% for all analytes at the same tested concentrations. The limit of quantitation is 25nM for the basic substances and 50nM for atovaquone. Several considerations regarding development and optimization of a method for determination of analytes with such a difference in physiochemical properties are discussed.

Authors

Niklas Lindegårdh

Other publications >>

Daniel Blessborn

Högskolan Dalarna; Kemiteknik
Other publications >>

Yngve Bergqvist

Högskolan Dalarna; Kemiteknik
Other publications >>

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    header: 
        identifier: oai:dalea.du.se:1203
        datestamp: 2021-04-15T13:01:54Z
        setSpec: SwePub-du
    metadata: 
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            @attributes: 
                version: 3.7
            recordInfo: 
                recordContentSource: du
                recordCreationDate: 2005-06-01
            identifier: 
                http://urn.kb.se/resolve?urn=urn:nbn:se:du-1203
                10.1093/chromsci/43.5.259
                15975245
            titleInfo: 
                @attributes: 
                    lang: eng
                title: Simultaneous quantification of the highly lipophilic atovaquone and the hydrophilic strong basic proguanil and its metabolites using a new mixed-mode SPE approach and Steep-Gradient LC
            abstract: 
A bioanalytical method is described for the simultaneous quantitative analysis of the highly lipophilic atovaquone and the strong basic proguanil with metabolites in plasma. The drugs are extracted from protein precipitated plasma samples on a novel mixed-mode solid-phase extraction (SPE) column containing carboxypropyl and octyl silica as functional groups. The analytes are further separated and quantitated using a steep-gradient liquid chromatograhic method on a Zorbax SB-CN column with UV detection at 245 nm. Two different internal standards (IS) are used in the method to compensate for both types of analytes. A structurally similar IS to atovaquone is added with acetonitrile to precipitate proteins from plasma. A structurally similar IS to proguanil and its metabolites is added with phosphate buffer before samples are loaded onto the SPE columns. A single elution step is sufficient to elute all analytes. The method is validated according to published guidelines and shows excellent performance. The within-day precisions expressed as relative standard deviation are lower than 5% for all analytes at three tested concentrations within the calibration range. The between-day precisions are lower than 13% for all analytes at the same tested concentrations. The limit of quantitation is 25nM for the basic substances and 50nM for atovaquone. Several considerations regarding development and optimization of a method for determination of analytes with such a difference in physiochemical properties are discussed.

            subject: 
                    @attributes: 
                        lang: eng
                        authority: uka.se
                    topic: 
                        Engineering and Technology
                        Chemical Engineering
                    @attributes: 
                        lang: swe
                        authority: uka.se
                    topic: 
                        Teknik och teknologier
                        Kemiteknik
            language: 
                languageTerm: eng
            genre: 
                publication/journal-article
                ref
            note: 
                Published
                3
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                    namePart: 
                        Lindegårdh
                        Niklas
                    role: 
                        roleTerm: aut
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                        type: personal
                        authority: du
                    namePart: 
                        Blessborn
                        Daniel
                    role: 
                        roleTerm: aut
                    affiliation: 
                        Högskolan Dalarna
                        Kemiteknik
                    nameIdentifier: dbl
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                        type: personal
                        authority: du
                    namePart: 
                        Bergqvist
                        Yngve
                    role: 
                        roleTerm: aut
                    affiliation: 
                        Högskolan Dalarna
                        Kemiteknik
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                dateIssued: 2005
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                titleInfo: 
                    title: Journal of Chromatographic Science
                identifier: 
                    0021-9665
                    1945-239X
                part: 
                    detail: 
                            @attributes: 
                                type: volume
                            number: 43
                            @attributes: 
                                type: issue
                            number: 5
                    extent: 
                        start: 259
                        end: 266
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                form: print
            typeOfResource: text