uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi. (Analytisk kemi)
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi. (Analytisk kemi)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
Visa övriga samt affilieringar
2009 (Engelska)Ingår i: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, nr 3, s. 291-297Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

This work presents the development and validation of a fully automated quantitative analysis method of melagatran, its prodrug ximelagatran, and its major metabolites for the study of drug behavior in biofluids. The method involves online sample clean-up and enrichment on a C4 capillary column followed by separation on a capillary C18 column. Electrospray ionization tandem mass spectrometric detection in positive ion mode was performed with multiple reactions monitoring of eight different transients, divided into two time segments with four transients each. The structural similarity, the complexity of the matrix (pig liver extract) and the formation of isobaric fragment ions, made efficient chromatographic separation necessary. The analysis method provides valid accuracy (<9%; RSD%), precision (<8%; RSD%), linearity (<1.2 nM–1 μM; R2 > 0.999), limit of quantitation (<3.6 nM), retention repeatability (<1.2%; RSD%), selectivity, as well as analyte and column stabilities over a wide concentration range.

Ort, förlag, år, upplaga, sidor
2009. Vol. 877, nr 3, s. 291-297
Nyckelord [en]
Online, solid phase extraction, liquid chromatography, mass spectrometry, ximelagatran, metabolites, pig liver
Nationell ämneskategori
Kemi
Identifikatorer
URN: urn:nbn:se:uu:diva-88170DOI: 10.1016/j.jchromb.2008.12.017ISI: 000262877500026PubMedID: 19117807OAI: oai:DiVA.org:uu-88170DiVA, id: diva2:139436
Tillgänglig från: 2009-01-22 Skapad: 2009-01-22 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
Ingår i avhandling
1. Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry
Öppna denna publikation i ny flik eller fönster >>Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry
2009 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Metabolism is the sum of all chemical processes with the purpose to maintain life, as well as enable reproduction, in a living organism. Through the study of metabolism, increased understanding of pharmacological mechanisms and diseases can be achieved. This thesis describes several ways of doing so, including targeted analysis of selected metabolites and investigations of systematic metabolic differences between selected groups through pattern recognition.

A method for exploring metabolic patterns in urine samples after intake of coffee or tea was developed. The methodology was later used with the aim to find biomarkers for prostate cancer and urinary bladder cancer.

Furthermore, a fully automated quantitative method was developed for concentration measurements of the double prodrug ximelagatran and its metabolites in pig liver. The method was then used to study the roll of active transporters in pig liver cells.

Moreover, a fundamental study was conducted to investigate how monitoring of small, doubly charged analytes can improve the limit of detection and precision in a quantitative method.

The techniques used for the experiments were liquid separation coupled to electrospray mass spectrometry. Extra efforts were made to make the separation and the ionization as compatible as possible to each other for increased quality of the collected data.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2009. s. 63
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 690
Nyckelord
liquid chromatography, mass spectrometry, tandem mass spectrometry, method development, capillary electrophoresis, electrospray ionization, time-of-flight, quantitation, metabolomics, metabonomics, pattern recognition, ximelagatran, melagatran, charge state
Nationell ämneskategori
Analytisk kemi
Forskningsämne
analytisk kemi
Identifikatorer
urn:nbn:se:uu:diva-110310 (URN)978-91-554-7663-2 (ISBN)
Disputation
2009-12-14, C4:301, BMC, Husargatan 3, Uppsala, 10:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2009-11-24 Skapad: 2009-11-10 Senast uppdaterad: 2009-11-24Bibliografiskt granskad
2. Quantitative Bioanalysis: Liquid separations coupled to targeted mass spectrometric measurements of bioactive compounds
Öppna denna publikation i ny flik eller fönster >>Quantitative Bioanalysis: Liquid separations coupled to targeted mass spectrometric measurements of bioactive compounds
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Performing quantitative analysis of targeted bioactive compounds in biological samples, such as blood plasma, cerebrospinal fluid or extracts from pig liver, put high demands on the ruggedness of the method acquiring the results. In addition to the complexity of the sample matrix, the bioactive compounds targeted for analysis usually have low levels of natural abundance, further increasing the demand on the analytical method sensitivity. Furthermore, quantitation of analytes at trace levels in the presence of large amounts of interfering species in biofluids must aim for repeatable precision, high accuracy ensuring the closeness to the true values, a linear response spanning over several orders of magnitude and low limits of quantitation to be valid for monitoring disease states in clinical analysis.

An analytical method most commonly follow a certain order of events, called the analytical chain, which includes; experimental planning, sampling, sample pre-treatment, separation of species, detection, evaluation, interpretation and validation, all equally important for the outcome of the results.

In this thesis, the scope has been to create novel methods, or to refine already existing methods, in order to achieve even better performances of the different events in the analytical chain.

One of the aspects has been to sample and enrich analytes in vivo by the use of solid supported microdialysis, giving the advantage of almost real-time monitoring of analyte levels within a living host with targeted selectivity due to the analyte affinity for solid particles. Another aspect to selectively clean and enrich analytes in a complex matrix has been developed and automated on-line by the use of a column-switching technique before the analytical separation. By using several steps of extraction and separation coupled on-line to selected detection by the use of a triple quadrupole mass spectrometer facilitates great selectivity of species. The mass spectrometer also gives the ability to distinguish between isotopically labelled analogues coeluting with the analytes yielding the necessary accuracy for quantitative evaluation.

Both development of analytical methods and clinical applications has been performed, as well as improvements of existing techniques, all to improve the quantitation of trace levels of targeted analytes in biofluids.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2008. s. 61
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 412
Nyckelord
Analytical chemistry, Method development, Enhanced microdialysis, Column switching, Liquid chromatography, Capillary electrophoresis, Electrospray ionization, Mass spectrometry, Triple quadrupole, Time-of-flight, Quantitation, Validation, Analytisk kemi
Nationell ämneskategori
Kemi
Identifikatorer
urn:nbn:se:uu:diva-8581 (URN)978-91-554-7135-4 (ISBN)
Disputation
2008-04-10, B22, BMC, Husargatan 3, Uppsala, 10:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2008-03-17 Skapad: 2008-03-17 Senast uppdaterad: 2013-06-20Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Sjöberg, Per Johan RagnarBergquist, Jonas

Sök vidare i DiVA

Av författaren/redaktören
Sjöberg, Per Johan RagnarBergquist, Jonas
Av organisationen
Institutionen för fysikalisk och analytisk kemiInstitutionen för farmaci
I samma tidskrift
Journal of chromatography. B
Kemi

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 1048 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf