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  • Results are reported for both 6-TGN and me-MP when the 6-TGN analysis is ordered

  • Analysis: 6-TGN (6-thioguanine nucleotides)
    & me-MP (methyl-mercaptopurine)
  • Relevant drugs: Azathioprine and 6-mercaptopurine
  • Sample material: Heparin whole blood, minimum 1.5 ml
  • Sampling time: Minimum 2 hrs after dose.
  • Storage: Store at 2-8°C until shipment (max 1 week)
  • Shipment: Ship at 2-8°C if possible. Alternatively, ship at ambient temperature. Avoid freezing. Samples should arrive in the laboratory within max 3 days.
  • Analytical method: LC-MS/MS • Instrumentation: Quattro micro API, Waters
  • Frequency of analysis: The analysis will normally be run 2-3 times a week (unless instrument down-time)
  • Measurement ranges: 6-TGN 0.5-20 µmol/L (packed erythrocytes)    •   me-MP 5.0 -200 µmol/L (packed erythrocytes)
  • Imprecision between series: 6-TGN CV ≤10%    •    me-MP CV ≤10%
  • Suggested therapeutic range (based on Crohns disease)
    • 6-TGN 3.5-5.0 µmol/L
    • me-MP above 50 µmol/L is associated with increased toxicity
  • Our reported concentration unit (µmol/L packed erythrocytes) may be compared with the unit usually reported in the literature (pmol/8×108 erythrocytes) by using the following tables: Comparison of 6-TGN and me-MP concentration units.
  • For further questions, please Contact us
  • Ordering of analysis: A prior arrangement is mandatory for ordering of analysis and shipment of 6-TGN samples to our laboratory from other countries than Norway. Specific agreements may be arranged by contacting us.
  • 6-TGN requisition forms for existing arrangements and projects may be downloaded here
  • More info on the relevant drugs: References are quoted on the Norwegian part of this website. For extensive info in English, a large number of online sources are available, like UpToDate etc etc.

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6-TGN & me-MP

6-TGN & me-MP background
Interpretation of analytical results

6-TGN & me-MP background

6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (me-MP) are metabolites of the thiopurines azathioprine and 6-mercaptopurine. Azathioprine is in use for the treatment of autoimmune diseases (e.g. Crohns disease), to prevent rejection after organ transplantation and on several other indications while 6-mercaptopurine is approved for the treatment of acute leukemia.

  • Monitoring of 6-TGN may be helpful to optimize the thiopurine treatment
    -but does not eliminate the need for careful hematological monitoring, as generally recommended.
  • 6-TGN levels in erythrocytes correlates with both therapeutic effect and toxicity.
  • High me-MP levels in erythrocytes are associated with toxicity.

Interpretation of analytical results

  • Steady state concentrations of 6-TGN in erythrocytes will be established during days to weeks on permanent dosing. Following cessation of medication the elimination of 6-TGN will be completed after several weeks, depending on the duration of treatment.
  • Thiopurine S-methyltransferase (TPMT) catalyzes the production of me-MP.
  • The TPMT activity is significantly reduced in some individuals due to genetic variability. Approximately 10% of the population inherits a heterozygote gene variant causing low TPMT activity, and approximately 1 in 300 have a gene variant causing almost absent TPMT activity.
  • Low or absent TPMT activity leads to negligible me-MP levels accompanying very high 6-TGN levels.
  • Serious adverse effects, mainly bone marrow suppression, will be more frequent in individuals with extreme 6-TGN levels.
  • It is generally recommended to perform genotyping or phenotyping of TPMT before onset of thiopurine treatment. EDTA blood may be shipped to our laboratory for TPMT genotyping
  • Considerably reduced renal function may lead to increased 6-TGN levels and risk of toxicity.
  • Drug interactions
    • 5-aminosalcylic acid (5-ASA) drugs may decrease the TPMT activity, thereby causing increased 6-TGN levels.
    • Allopurinol is an inhibitor of xanthine dehydrogenase and may increase the 6-TGN levels. In addition, allopurinol may decrease the me-MP levels.
    • Infliximab may increase the 6-TGN levels, this effect is reversible.

For further questions, please Contact us.

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Sist oppdatert 29.juni 2022 av Stein Bergan