- 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. UpToDate is one that we favor.
6-TGN & me-MP
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.
Authors NTV & StB (Updated 28.12.17)