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Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
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2002 In: European journal of clinical pharmacology, Vol. 58, 19-27 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 58, 19-27 p.
Identifiers
URN: urn:nbn:se:uu:diva-90193OAI: oai:DiVA.org:uu-90193DiVA: diva2:162459
Available from: 2003-04-24 Created: 2003-04-24Bibliographically approved
In thesis
1. Development of Field-adapted Analytical Methods for the Determination of New Antimalarial Drugs in Biological Fluids
Open this publication in new window or tab >>Development of Field-adapted Analytical Methods for the Determination of New Antimalarial Drugs in Biological Fluids
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis deals with the development of analytical methods for the determination of new antimalarial drugs in biological fluids. The goal was to develop methods that facilitate clinical studies performed in the field, such as capillary blood sampling onto sampling paper.

Methods for the determination of atovaquone (ATQ) in plasma, whole blood and capillary blood applied onto sampling paper were developed and validated.

Automated solid-phase extraction (SPE) and liquid chromatography (LC) with UV absorbance detection was used to quantify ATQ. Venous blood contained higher levels of ATQ than capillary blood after a single dose of Malarone (ATQ + proguanil).

Ion-pairing LC was used to separate amodiaquine (AQ), chloroquine (CQ) and their metabolites on a CN-column. A method for quantification of AQ, CQ and their metabolites in capillary blood applied onto sampling paper was developed and validated. Perchloric acid and acetonitrile were used to facilitate the extraction of the analytes from the sampling paper. The liquid extract was further cleaned by SPE.

Methods for the determination of piperaquine (PQ) in plasma and whole blood using SPE and LC were developed and validated. Addition of trichloroacetic acid (TCA) to the samples prior to injection into the LC-system significantly enhanced the efficiency for the PQ peak. Serum and whole blood contained higher levels (about 300 nM) of PQ than plasma (about 200 nM) after a single oral dose of 340 mg PQ. This indicates that PQ may be taken up in the leucocytes and thrombocytes.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 64 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 823
Keyword
Analytical chemistry, LC, liquid chromatography, biological samples, SPE, solid phase extraction, validation, antimalarial drugs, amodiaquine, piperaquine, atovaquone, dried blood spots, Analytisk kemi
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-3346 (URN)91-554-5573-5 (ISBN)
Public defence
2003-05-16, Teknikdalens Aula, Teknikdalen, Borlänge, Borlänge, 13:15
Opponent
Supervisors
Available from: 2003-04-24 Created: 2003-04-24Bibliographically approved

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