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Development and validation of a bioanalytical method using automated solid-phase extraction and LC-UV for the simultaneous determination of lumefantrine and its desbutyl metabolite in plasma
Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand; Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, Oxford, UK.
Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Dalarna University College, S-781 88 Borlänge, Sweden.
Dalarna University College, S-781 88 Borlänge, Sweden.
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2005 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 37, no 5, 1081-1088 p.Article in journal (Refereed) Published
Abstract [en]

A bioanalytical method for the determination of lumefantrine (LF) and its metabolite desbutyl-lumefantrine (DLF) in plasma by solid-phase extraction (SPE) and liquid chromatography has been developed. Plasma proteins were precipitated with acetonitrile:acetic acid (99:1, v/v) containing a DLF analogue internal standard before being loaded onto a octylsilica (3 M Empore) SPE column. Two different DLF analogues were evaluated as internal standards. The compounds were analysed by liquid chromatography UV detection on a SB-CN (250 mm x 4.6 mm) column with a mobile phase containing acetonitrile-sodium phosphate buffer pH (2.0; 0.1 M) (55:45, v/v) and sodium perchlorate 0.05 M. Different SPE columns were evaluated during method development to optimise reproducibility and recovery for LF, DLF and the two different DLF analogues. The within-day precisions for LF were 6.6 and 2.1% at 0.042 and 8.02 microg/mL, respectively, and for DLF 4.5 and 1.5% at 0.039 and 0.777 microg/mL, respectively. The between-day precisions for LF were 12.0 and 2.9% at 0.042 and 8.02 microg/mL, respectively, while for DLF 0.7 and 1.2% at 0.039 and 0.777 microg/mL, respectively. The limit of quantification was 0.024 and 0.021 microg/mL for LF and DLF, respectively. Different amounts of lipids in plasma did not affect the absolute recovery of LF or DLF.

Place, publisher, year, edition, pages
2005. Vol. 37, no 5, 1081-1088 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-108746DOI: 10.1016/j.jpba.2004.07.041PubMedID: 15862688OAI: oai:DiVA.org:uu-108746DiVA: diva2:240702
Available from: 2009-09-29 Created: 2009-09-29 Last updated: 2013-08-01Bibliographically approved
In thesis
1. Development of Analytical Methods for the Determination of Antimalarials in Biological Fluids
Open this publication in new window or tab >>Development of Analytical Methods for the Determination of Antimalarials in Biological Fluids
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to develop analytical methods for measuring antimalarial drugs in biological fluids. Solid phase extraction (SPE) was used for the enrichment and purification of the drugs. Automatic extraction procedures using a SPE robot were developed to reduce the workload for the analyst and to minimize variations in the extraction procedure. Liquid chromatography (LC) with either UV or mass spectrometric (MS) detection was used to determine sample concentrations.

Determination of Pyronaridine in whole blood utilised a weak cation exchanger to extract Pyronaridine from blood. To improve LC separation between Pyronaridine and the internal standard, ion-pairing was utilized.

For the simultaneous quantification of the highly lipophilic Atovaquone and the strong basic drug Proguanil with metabolites, a novel mixed mode solid phase extraction column was used. It combines the properties of a carboxylic acid (CBA) column and a non-polar octyl-silica (C8) column to extract the compounds from plasma; it also required a gradient LC separation.

Stability is an important factor when developing new methods. A new approach was used to evaluate the stability of Amodiaquine in blood and plasma. This included the use of a stability marker, a stable compound which was added together with Amodiaquine when preparing the stability samples. This eliminated between-run variations and variations associated with preparation of new stock solutions.

Lumefantrine (LF) is one of the active components in a new drug combination recommended by the World Health Organization as a replacement for older drugs which have lost their effect. The first of the two methods described for this compound is the determination of LF and a possible metabolite in plasma with a calibration range suitable for pharmacokinetic studies. In the second method, a capillary sampling technique is used where the blood is dried on a sampling paper and sent to the laboratory where the extraction and determination of LF concentrations take place. This method facilitates sample collection and will enable drug efficacy studies conducted in rural settings.

To monitor a current change in treatment policy and self medication, a screening assay was developed. Its purpose is to be a complement to interviewing patients about their previous medication (in the previous few weeks) and to detect some of the more common drugs which might have been used.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 52 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 676
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-108767 (URN)978-91-554-7620-5 (ISBN)
Public defence
2009-11-12, Clas Ohlson room, Humanistgatan 2, Tenoren, Högskolan Dalarna, Borlänge, 13:00 (Swedish)
Opponent
Supervisors
Note
Paper 6. as ManuscriptAvailable from: 2009-10-22 Created: 2009-09-29 Last updated: 2009-10-22Bibliographically approved

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