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Determination of pyronaridine in whole blood by automated solid-phase extraction and high-performance liquid chromatography
Dalarna University College, Borlange, Sweden. Department of Analytical Chemistry, Uppsala University, Uppsala, Sweden.
Dalarna University College, Borlange, Sweden. Department of Analytical Chemistry, Uppsala University, Uppsala, Sweden.
Unit of Tropical Pharmacology, Division of Clinical Pharmacology and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
Unit of Tropical Pharmacology, Division of Clinical Pharmacology and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
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2003 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 25, no 3, 264-270 p.Article in journal (Refereed) Published
Abstract [en]

A new extraction procedure for the analysis of pyronaridine in whole blood is presented. A weak cation exchanger with a carboxylic acid (CBA) sorbent was found to be a suitable solid phase sorbent for the extraction of pyronaridine. High-performance liquid chromatography with UV detection at 278 nm and an electrochemical detector at +0.75 V is used. The electrochemical detector gives higher selectivity than the UV detector. The separation was performed using a C18 reversed phase column with mobile phase of acetonitrile-phosphate buffer (0.01 mol/L, pH 2.5)- sodium perchlorate (1.0 mol/L; 22:77:1, v/v/v). The within-day RSDs were below 5% at all concentration levels between 75 nmol/L and 1500 nmol/L, and the between-day RSDs were below 14% at all concentration levels. The limit of quantification was about 50 nmol/L in 1000 microL whole blood with an RSD of 20% or less on a day-to-day basis. The stability of pyronaridine is increased if the pH is less than 3 in water solutions. In whole blood, the concentration decreases by about 10% for each freeze-thaw cycle performed. At room temperature (about 22 degrees C), pyronaridine concentration in whole blood decreases by about 10% within 12 to 24 hours.

Place, publisher, year, edition, pages
2003. Vol. 25, no 3, 264-270 p.
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-48733PubMedID: 12766551OAI: oai:DiVA.org:uu-48733DiVA: diva2:76639
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-05Bibliographically 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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