硫嘌呤代谢物在血液样本中的稳定性有限：在研究和临床实践中相关。

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

机构信息

Clinical Pharmacology and Pharmacy, VU University Medical Centre, Amsterdam, The Netherlands.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 1;878(19):1437-42. doi: 10.1016/j.jchromb.2010.03.004. Epub 2010 Mar 12.

DOI:10.1016/j.jchromb.2010.03.004

PMID:20399153

Abstract

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 day 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.

摘要

背景

监测硫嘌呤代谢物 6-硫鸟嘌呤核苷酸（6-TGN）和 6-甲基巯基嘌呤（6-MMP）可用于评估 IBD 患者的依从性并解释不良反应。剂量、代谢物浓度与治疗效果或毒性之间的相关性存在矛盾。由于分析基质和分析程序差异很大，因此研究受到分析问题的复杂化。此外，硫嘌呤代谢物的稳定性尚未得到很好的记录，但对于解释分析结果至关重要。因此，我们前瞻性地研究了标准储存条件下血液样本中代谢物的稳定性。

方法

在室温（22°C）和冷藏（4°C）下研究了稳定性，在 1 周内进行了研究，并在 6 个月的储存期间分析了冷冻样品（-20°C，-80°C）。每个研究期间分析了 10 个患者样本。

结果

在室温或冷藏条件下储存 7 天，6-TGN 浓度中位数分别显著下降至 53%和 90%。6-MMP 浓度中位数在第 7 天分别显著下降至 55%和 86%。与基线值相比，-20°C 储存的样本中两种 6-TGN 和 6-MMP 均明显下降。在-80°C 下，与基线值相比，仅 6-MMP 的值显示出显著下降。