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Development and validation of an automated solid-phase extraction and liquid chromatographic method for determination of lumefantrine in capillary blood on sampling paper
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, Oxford, UK.
Dalarna University College, Borlange, Sweden. .
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2007 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 45, no 2, 282-287 p.Article in journal (Refereed) Published
Abstract [en]

A bioanalytical method for the determination of lumefantrine in 100 μl blood applied onto sampling paper, by solid-phase extraction and liquid chromatography, has been developed and validated. Whatman 31 ET Chr sampling paper was pre-treated with 0.75 M tartaric acid before sampling capillary blood to enable a high recovery of lumefantrine. Lumefantrine was extracted from the sampling paper, then further purified using solid-phase extraction and finally quantified with HPLC. The between-day variation was below 10% over the range 0.4-25 μM. The lower limit of quantification was 0.25 μM in 100 μl capillary blood. No decrease in lumefantrine concentration in dried blood spot is seen after 4 months storage at 22 °C. The method was also evaluated in field samples from patients in Tanzania after treatment with lumefantrine/artemether. Lumefantrine could be estimated accurately enough to assess bioavailability and treatment compliance on day 7 (i.e. 4 days after the last dose) after a standard regimen with the lumefantrine/artemether combination.

Place, publisher, year, edition, pages
2007. Vol. 45, no 2, 282-287 p.
Keyword [en]
Lumefantrine, Sampling paper, Dried blood spots, Capillary blood, Antimalarial drugs, Solid-phase extraction, Liquid chromatography
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-11919DOI: 10.1016/j.jpba.2007.07.015ISI: 000250888700014PubMedID: 17719735OAI: oai:DiVA.org:uu-11919DiVA: diva2:39688
Available from: 2007-11-06 Created: 2007-11-06 Last updated: 2017-12-11Bibliographically 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
2. Development and Validation of Bioanalytical Methods: Application to Melatonin and Selected Anti-Infective Drugs
Open this publication in new window or tab >>Development and Validation of Bioanalytical Methods: Application to Melatonin and Selected Anti-Infective Drugs
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes bioanalytical methods for measuring melatonin and some anti-infective drugs in biological fluids. Solid-phase extraction (SPE) or protein precipitation was used for enrichment and purification of the analytes and Liquid Chromatography (LC) was used to analyze the samples. Developed methods were validated according to international guidelines.

Melatonin is a hormone secreted by the pineal gland with a robust circadian rhythm. Bioanalytical methods for determination of melatonin in plasma and saliva have been developed which were used for monitoring melatonin levels in volunteers and patients suffering from sleep related diseases.

Eflornithine (DFMO) is a chiral drug used for the treatment of human African trypanosomiasis. A bioanalytical method for determination of the DFMO enantiomers in plasma, after precolumn derivatization with o-phtalaldehyde and N-acetyl-L-cystein has been developed. The method has been used to study the L- and D-DFMO pharmacokinetics, in order to investigate the possible development of an oral treatment of DFMO.

A method for simultaneous determination of three antiretroviral drugs i.e. Lamivudine (3TC), Zidovudine (AZT) and Nevirapine (NVP) in dried blood spots (DBS) was developed. The method was used for drug determination in two subjects after receiving standard antiretroviral treatment. The method seemed well suitable for the determination of 3TC and NVP and in some extent for AZT.

Lumefantrine (LF) is one of the active components in a new fixed drug combination recommended by the WHO as a replacement to older drugs that has lost their effect. A method for the determination of LF in DBS was developed. The method is suitable for monitoring of drug treatment in rural settings.

Tafenoquine is a new promising antimalarial drug under development. A method for the determination of Tafenoquine in plasma and in DBS is described. The method may be useful in future clinical studies in laboratory environment as well as in rural settings.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 53 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 773
Keyword
african trypanosomiasis, melatonin, malaria, antiretroviral drugs, lumefantrine, tafenoquine, lamivudine, nevirapine, zidovudine, sampling paper, dried blood spots, capillary blood, antimalarial drugs, solid-phase extraction, liquid chromatography
National Category
Chemical Sciences
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-131519 (URN)978-91-554-7908-4 (ISBN)
Public defence
2010-11-16, Clas Ohlson room, Tenoren, Högskolan Dalarna, Borlänge, 13:00 (Swedish)
Opponent
Supervisors
Note
Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 703Available from: 2010-10-26 Created: 2010-10-04 Last updated: 2011-03-21Bibliographically approved

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