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Determination of lamivudine, zidovudine and nevirapine, in capillary blood sampled on filter paper, by liquid chromatography
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
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.
2009 (English)In: Journal of Chromatographic Science, ISSN 0021-9665, E-ISSN 1945-239X, Vol. 47, no 10, 855-862 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2009. Vol. 47, no 10, 855-862 p.
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96868ISI: 000271527500002OAI: oai:DiVA.org:uu-96868DiVA: diva2:171592
Available from: 2008-03-19 Created: 2008-03-19 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Drug Analysis: Bioanalytical Method Development and Validation
Open this publication in new window or tab >>Drug Analysis: Bioanalytical Method Development and Validation
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes bioanalytical methods for drug determination in biological matrixes, with drugs in focus used against diseases largely affecting low-income countries.

Solid-phase extraction is used for sample cleanup, and processed samples are analyzed by liquid chromatography. Developed bioanalytical methods are validated according to international guidelines.

Eflornithine (DFMO) is a chiral drug, used for treating human African trypanosomiasis. A bioanalytical method for determination of DFMO enantiomers in plasma is presented. The enantiomers are detected by evaporative light-scattering detection. The method has been applied to determination of D-DFMO and L-DFMO in rats, after intravenous and oral administration of racemic DFMO. It is concluded that DFMO exhibits enantioselective absorption, with the more potent enantiomer L-DFMO being less favored.

Sulfadoxine (SD) and sulfamethoxazole (SM) are sulfa-drugs used for malaria and pneumonia respectively. Two methods are described for simultaneous determination of SD and SM in capillary blood sampled on filter paper. The former method allows direct injection of extracts from dried blood spots (DBS), while for the latter method solid-phase extraction is added. Pre-analytical factors contributing to measurement uncertainty is also discussed, and it is concluded that it is of high importance that homogeneity in type of sampling paper and sampling volume is assured.

Piperaquine (PQ) is an antimalarial, increasingly used in artemisinin combination therapy. A method for determination of piperaquine in DBS is presented. By using a monolithic LC column, a very short LC analysis of two minutes per sample is achieved.

A method for simultaneous determination of three antiretroviral drugs i.e. lamivudine (3TC), zidovudine (AZT) and nevirapine (NVP), in DBS samples is described. The method is applied to drug determination in two subjects after receiving standard antiretroviral treatment. Conclusion is that the method is suitable for determination of 3TC and NVP, and to some extent for AZT.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 406
Keyword
Analytical chemistry, African trypanosomiasis, calibration model, chiral chromatography, dried blood spots, eflornithine, evaporative light-scattering detection, HIV/AIDS, lamivudine, liquid chromatography, malaria, nevirapine, piperaquine, pneumonia, solid-phase extraction, sulfadoxine, sulfamethoxazole, validation, zidovudine, Analytisk kemi
Identifiers
urn:nbn:se:uu:diva-8547 (URN)978-91-554-7125-5 (ISBN)
Public defence
2008-04-18, Clas Ohlson room, Tenoren, Högskolan Dalarna, Borlänge, 13:00 (English)
Opponent
Supervisors
Available from: 2008-03-19 Created: 2008-03-19 Last updated: 2009-03-24Bibliographically 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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