A design for external quality assessment for the analysis of thiopurine drugs: pitfalls and opportunities

Karen Robijns*, Matthijs van Luin, Rob T. P. Jansen, Cees Neef, Daan J. Touw

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)


Background: For the analysis of 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine ribonucleotides (6-MMPR), no external quality assessment scheme (EQAS) is currently available and no quality control samples can be made because of the absence of pure substances. An experimental design is tested to compare laboratory analytical results. Methods: In this EQAS, participating laboratories were asked to select patient samples from their routine analysis and exchange these with a coupled laboratory. Because of large differences in results between laboratories, all standard operating procedures were reviewed, revealing that the origin of these differences could be in the method of hydrolysis and the preparation of calibrators. To investigate the contribution of the calibrators to these differences, one participating laboratory was asked to prepare a batch of calibrators to be shipped to the participating laboratories for analysis. Results: Results for 6-TGN differed more between laboratories, compared with results for 6-MMPR. For 6-TGN and 6-MMPR 43% and 24% of the results, respectively, were out of the 80%-120% range. When correcting the results from the exchange of the patient samples with the results of the calibrators, the mean absolute difference for 6-TGN improved from 24.8% to 16.3% (p < 0.001), while the results for 6-MMPR worsened from 17.3% to 20.0% (p = 0.020). Conclusions: This first EQAS for thiopurine drugs shows that there is a difference between laboratories in the analysis of 6-TGN, and to a lesser extent in the analysis of 6-MMPR. This difference for 6-TGN can partially be explained by the use of in-house-prepared calibrators that differ among the participants.
Original languageEnglish
Pages (from-to)1715-1721
Number of pages7
JournalClinical Chemistry and Laboratory Medicine
Issue number10
Publication statusPublished - 1 Oct 2018


  • external quality assessment scheme
  • harmonization
  • thiopurine drugs

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