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Monitoring of thiopurine metabolites - A high-performance liquid chromatography method for clinical use
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
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2013 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 75, 145-152 p.Article in journal (Refereed) Published
Abstract [en]

A high-performance liquid chromatography method capable of measuring thiopurine mono-, di-, and triphosphates separately in red blood cells (RBCs) was developed. RBCs were isolated from whole blood using centrifugation. Proteins were precipitated using dichloromethane and methanol. The thioguanine nucleotides (TGNs) were derivatised using potassium permanganate before analysis. Analytes were separated by ion-pairing liquid chromatography using tetrabutylammonium ions and detected using UV absorption and fluorescence. The method was designed for use in clinical trials. Ten patient samples were analysed to demonstrate clinical application and to establish pilot ranges for all analytes. less thanbrgreater than less thanbrgreater thanThe method measured thioguanosine mono-(TGMP), di-(TGDP), and triphosphate (TGTP), as well as methylthioinosine mono- (meTIMP), di- (meTIDP) and triphosphate (meTITP) in RBCs collected from patients treated with thiopurine drugs (azathioprine, 6-mercaptopurine, and 6-thioguanine). less thanbrgreater than less thanbrgreater thanLOQ was 0.3, 3, 2, 30, 30 and 40 pmol/8 x 10(8) RBC, for TGMP, TGDP, TGTP, meTIMP, meTIDP and meTITP, respectively. Between-day precision were below 14% for all analytes at all concentrations and samples were stable at 4 degrees C for 8 h after sampling.

Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 75, 145-152 p.
Keyword [en]
Inflammatory bowel disease (IBD), HPLC, Nucleotide, Acute lymphoid leukaemia, Pharmacogenetics
National Category
Engineering and Technology
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URN: urn:nbn:se:liu:diva-89732DOI: 10.1016/j.jpba.2012.11.027ISI: 000314332500019OAI: oai:DiVA.org:liu-89732DiVA: diva2:609383
Note

Funding Agencies|Swedish Cancer Society||Swedish Childhood Cancer Foundation||Swedish Medical Research Council||

Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2017-12-06

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Vikingsson, SvanteAlmer, SvenPeterson, CurtCarlsson, BjörnJosefsson, Martin

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