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Determination of eflornithine enantiomers in plasma by precolumn derivatization with o-phthalaldehyde-N-acetyl-l-cysteine and liquid chromatography with UV detection
Sahlgrenska Academy at University of Gothenburg, Unit for Pharmacokinetics and drug metabolism, Göteborg, Sweden.
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.
Sahlgrenska Academy at University of Gothenburg, Unit for Pharmacokinetics and drug metabolism, Göteborg, Sweden.
Sahlgrenska Academy at University of Gothenburg, Unit for Pharmacokinetics and drug metabolism, Göteborg, Sweden .
2010 (English)In: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 24, no 7, 768-773 p.Article in journal (Refereed) Published
Abstract [en]

A bioanalytical method for indirect determination of eflornithine enantiomers in 75 mu L human plasma has been developed and validated. L- and D-eflornithine were derivatized with o-phthalaldehyde and N-acetyl-L-cysteine to generate diastereomers which were separated on two serially connected Chromolith Performance columns (RP-18e 100 x 4.6 mm i.d.) by a isocratic flow followed by a gradient flow for elution of endogenous compounds. The diastereomers were detected with UV (340 nm). The between-day precisions for L- and D-eflornithine in plasma were 8.4 and 2.3% at 3 mu m, 4.0 and 5.1% at 400 mu m, and 2.0 and 3.7% at 1000 mu m. The lower limit of quantification was determined to be 1.5 mu m, at which precision was 14.9 and 9.9% for 1- and D-eflornithine, respectively.

Place, publisher, year, edition, pages
2010. Vol. 24, no 7, 768-773 p.
Keyword [en]
eflornithine, chiral separation, Human African sleeping sickness, cancer
National Category
Other Basic Medicine Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-131517DOI: 10.1002/bmc.1361ISI: 000279367900013OAI: oai:DiVA.org:uu-131517DiVA: diva2:354652
Available from: 2010-10-04 Created: 2010-10-04 Last updated: 2017-12-12Bibliographically approved
In thesis
1. 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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