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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Liquid chromatography-tandem mass spectrometry quantification of 6-thioguanine in DNA using endogenous guanine as internal standard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Increments in DNA-thioguanine level during thiopurine enhanced maintenance therapy of acute lymphoblastic leukemia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Selection criteria for assembling a pediatric cancer predisposition syndrome gene panel

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Thiopurines are S-substituted antimetabolites that are widely used in the treatment of hematological malignancies and as immunosuppressants. Because of extensive inter-individual variation in drug disposition and the significant toxicity associated with thiopurine therapy, there is a need for improved individualized treatment. We here present a fast and sensitive method for quantifying the pharmacological end-point of thiopurines, 6-thioguanine (TG) in chromosomal DNA. Purine nucleobases are released from DNA, etheno-derivatized with chloroacetaldehyde, separated by HILIC and quantified by tandem mass spectrometry using endogenous chromosomal guanine as internal standard. The method is linear up to at least 10 pmol TG/μg DNA and the limit of detection and quantification are 4.2 and 14.1 fmol TG/μg DNA, respectively. The matrix (DNA) had no effect upon quantification of TG. SPE recovery was estimated at 63% (RSD 26%), which is corrected for by the internal standard resulting in stable quantification. The TG levels found were above the LOQ in 18 out of 18 childhood leukemia patients on 6-mercaptopurine/methotrexate maintenance therapy (median 377, range 45-1190 fmol/μg DNA) with intra- and inter-day RSDs of less than 11%. The method uses 2 μg DNA/sample, which can easily be obtained from these patients.
OriginalsprogEngelsk
TidsskriftJournal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Vol/bind881-882
Sider (fra-til)115-8
Antal sider4
ISSN1570-0232
DOI
StatusUdgivet - 2012

ID: 36784892