Limited stability of thiopurine metabolites in blood samples: Relevant in research and clinical practise

被引：27

作者：

de Graaf, P. ^{[1
]}

Vos, R. M. ^{[1
]}

de Boer, N. H. K. ^{[1
]}

Sinjewel, A. ^{[1
]}

Jharap, B. ^{[1
]}

Mulder, C. J. J. ^{[1
]}

van Bodegraven, A. A. ^{[1
]}

Veldkamp, A. I. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands

来源：

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2010年 / 878卷 / 19期

关键词：

Inflammatory bowel disease; Azathioprine; 6-Mercaptopurine; Clinical pharmacology; Therapeutic drug monitoring; 6-Thioguanine; 6-Thioguanine nucleotides; 6-Methylmercaptopurine; Chemical stability; Patient blood samples; INFLAMMATORY-BOWEL-DISEASE; METHYLTRANSFERASE ACTIVITY; 6-THIOGUANINE NUCLEOTIDES; 6-MERCAPTOPURINE THERAPY; AZATHIOPRINE THERAPY; DNA; PHARMACOLOGY; EFFICACY;

D O I：

10.1016/j.jchromb.2010.03.004

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Background Monitoring of thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) is used to assess compliance and explain adverse reactions in IBD-patients Correlations between dosage, metabolite concentrations and therapeutic efficacy or toxicity are contradictive Research is complicated by analytical problems as matrices analyzed and analytical procedures vary widely Moreover, stability of thiopurine metabolites is not well documented, yet pivotal for interpretation of analytical outcomes. Therefore, we prospectively investigated metabolite stability in blood samples under standard storage conditions Methods Stability at room temperature and refrigeration (22 degrees C, 4 degrees C) was investigated during 1 week and frozen samples (-20 degrees C, -80 degrees C) were analyzed during 6 months storage Ten patient samples were analyzed for each study period Results Median 6-TGN concentrations on clay 7 decreased significantly to 53% and 90% during storage at ambient temperature or refrigeration Median 6-MMP concentrations on day 7 decreased significantly to 55% and 86%, respectively Samples stored at -20 degrees C also showed significant decreases in both 6-TGN and 6-MMP in comparison with baseline values At -80 degrees C, only 6-MMP showed a significant decrease in values compared to baseline. Conclusion The stability of thiopurine metabolites is clearly a limiting factor in studies investigating utilisation of TDM and correlations with therapeutic outcome in IBD-patients This has to be accounted for in clinical practice and (multi-center) trials investigating thiopurine drugs (C) 2010 Published by Elsevier B.V.

引用

页码：1437 / 1442

页数：6

共 33 条

[1] Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease [J].