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
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10.1093/chromsci/43.5.259Keyword: Engineering and Technology,
Chemical Engineering,
Teknik och teknologier,
KemiteknikPublication year: 2005Relevant Sustainable Development Goals (SDGs):
The SDG label(s) above have been assigned by OSDG.aiAbstract: 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
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Daniel Blessborn
Högskolan Dalarna; Kemiteknik
Other publications
>>
Yngve Bergqvist
Högskolan Dalarna; Kemiteknik
Other publications
>>
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identifier: oai:dalea.du.se:1203
datestamp: 2021-04-15T13:01:54Z
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http://urn.kb.se/resolve?urn=urn:nbn:se:du-1203
10.1093/chromsci/43.5.259
15975245
titleInfo:
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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
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lang: swe
authority: uka.se
topic:
Teknik och teknologier
Kemiteknik
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Published
3
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Lindegårdh
Niklas
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Blessborn
Daniel
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Högskolan Dalarna
Kemiteknik
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Bergqvist
Yngve
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Högskolan Dalarna
Kemiteknik
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title: Journal of Chromatographic Science
identifier:
0021-9665
1945-239X
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type: volume
number: 43
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