PMID- 20399153
OWN - NLM
STAT- MEDLINE
DCOM- 20100826
LR  - 20171116
IS  - 1873-376X (Electronic)
IS  - 1570-0232 (Linking)
VI  - 878
IP  - 19
DP  - 2010 Jun 1
TI  - Limited stability of thiopurine metabolites in blood samples: relevant in 
      research and clinical practise.
PG  - 1437-42
LID - 10.1016/j.jchromb.2010.03.004 [doi]
AB  - 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.
CI  - Copyright 2010. Published by Elsevier B.V.
FAU - de Graaf, P
AU  - de Graaf P
AD  - Clinical Pharmacology and Pharmacy, VU University Medical Centre, Amsterdam, The 
      Netherlands. Peer.deGraaf@vumc.nl
FAU - Vos, R M
AU  - Vos RM
FAU - de Boer, N H K
AU  - de Boer NH
FAU - Sinjewel, A
AU  - Sinjewel A
FAU - Jharap, B
AU  - Jharap B
FAU - Mulder, C J J
AU  - Mulder CJ
FAU - van Bodegraven, A A
AU  - van Bodegraven AA
FAU - Veldkamp, A I
AU  - Veldkamp AI
LA  - eng
PT  - Journal Article
DEP - 20100312
PL  - Netherlands
TA  - J Chromatogr B Analyt Technol Biomed Life Sci
JT  - Journal of chromatography. B, Analytical technologies in the biomedical and life 
      sciences
JID - 101139554
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
SB  - IM
MH  - Chromatography, High Pressure Liquid/methods
MH  - Drug Stability
MH  - Humans
MH  - Inflammatory Bowel Diseases
MH  - Mercaptopurine/*analogs & derivatives/blood/metabolism
MH  - Reproducibility of Results
MH  - Specimen Handling/*methods
MH  - Statistics, Nonparametric
MH  - Thioguanine/*blood/metabolism
EDAT- 2010/04/20 06:00
MHDA- 2010/08/27 06:00
CRDT- 2010/04/20 06:00
PHST- 2009/09/22 00:00 [received]
PHST- 2010/03/01 00:00 [revised]
PHST- 2010/03/04 00:00 [accepted]
PHST- 2010/04/20 06:00 [entrez]
PHST- 2010/04/20 06:00 [pubmed]
PHST- 2010/08/27 06:00 [medline]
AID - S1570-0232(10)00138-8 [pii]
AID - 10.1016/j.jchromb.2010.03.004 [doi]
PST - ppublish
SO  - 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.