liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping Sweden.
2016 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 119, 1-9 p.Article in journal (Refereed) Published
Abstract [en]

The analgesic drug tramadol and its metabolites are chiral compounds, with the (+)- and (-)-enantiomers showing different pharmacological and toxicological effects. This novel enantioselective method, based on LC-MS/MS in reversed phase mode, enabled measurement of the parent compound and its three main metabolites O-desmethyltramadol, N-desmethyltramadol and N,O-didesmethyltramadol simultaneously. Whole blood samples of 0.5g were fortified with internal standards (tramadol-(13)C-D3 and O-desmethyl-cis-tramadol-D6) and extracted under basic conditions (pH 11) by liquid-liquid extraction. Chromatography was performed on a chiral alpha-1-acid glycoprotein (AGP) column preceded by an AGP guard column. The mobile phase consisted of 0.8% acetonitrile and 99.2% ammonium acetate (20mM, pH 7.2). A post-column infusion with 0.05% formic acid in acetonitrile was used to enhance sensitivity. Quantitation as well as enantiomeric ratio measurements were covered by quality controls. Validation parameters for all eight enantiomers included selectivity (high), matrix effects (no ion suppression/enhancement), calibration model (linear, weight 1/X(2), in the range of 0.25-250ng/g), limit of quantitation (0.125-0.50ng/g), repeatability (2-6%) and intermediate precision (2-7%), accuracy (83-114%), dilution integrity (98-115%), carry over (not exceeding 0.07%) and stability (stable in blood and extract). The method was applied to blood samples from a healthy volunteer administrated a single 100mg dose and to a case sample concerning an impaired driver, which confirmed its applicability in human pharmacokinetic studies as well as in toxicological and forensic investigations.

Place, publisher, year, edition, pages
2016. Vol. 119, 1-9 p.
Keyword [en]
Enantiomer; LC–MS/MS; N, O-didesmethyltramadol; N-desmethyltramadol; O-desmethyltramadol; Tramadol
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:liu:diva-125284DOI: 10.1016/j.jpba.2015.11.012ISI: 000370211900001PubMedID: 26625281OAI: oai:DiVA.org:liu-125284DiVA: diva2:904613
Note

Funding agencies:The National Board of Forensic Medicine in Sweden funded this work.

Available from: 2016-02-19 Created: 2016-02-19 Last updated: 2016-03-09

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Haage, PernillaKronstrand, RobertCarlsson, BjörnJosefsson, Martin
By organisation
Division of Drug ResearchFaculty of Medicine and Health SciencesDepartment of Clinical PharmacologyDepartment of Physics, Chemistry and BiologyFaculty of Science & Engineering
In the same journal
Journal of Pharmaceutical and Biomedical Analysis
Analytical Chemistry

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 211 hits
ReferencesLink to record
Permanent link

Direct link