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- 6MP Metabolites
- 6TG Metabolites
- Azathioprine Metabolites
- Mercaptopurine Metabolites
This assay measures the red-cell concentration of 6-MMP (formed from 6-MP by thiopurine methyltransferase) and also measures the concentration of the resulting 6-TG after removal of the mono-, di-, or tri-phosphates from the various 6-thioguanine nucleotides. Once thiopurine therapy has been undertaken and an equilibrated drug level is achieved (usually three to six months), literature suggests that the measurement of thiopurine metabolites is warranted in the following situations:
1. Unresponsive patients to rule out (a) patient noncompliance (low 6-MMP and low 6-TG in those not taking medications), (b) those with diversion of metabolites away from 6-TG production (low 6-TG and normal or increased 6-MMP), (c) those with refractory to treatment (adequate 6-TG but lack of clinical response), and (d), those with excessive 6-MMP (or increased 6-MMP:6-TG ratio with adequate 6-TG) leading to increased hepatotoxicity.
2. Clinically responsive patients to look for excessive levels of either 6-MMP or 6-TG to avoid toxicity.
This test should only be performed for patients currently on thiopurine therapy. This therapy includes administration of azathioprine or mercaptopurine. This test may not be useful in patients with autoimmune hepatitis.
Whole blood washing and red blood cell harvesting/counting. Liquid chromatography/tandem mass spectrometry (LC/MS-MS) after acidic hydrolysis.
*Chevaux JB, Peyrin-Biroulet L, Sparrow MP. Optimizing thiopurine therapy in inflammatory bowel disease. Inflamm Bowel Dis. 2011 Jun; 17(6):1428-1435.
For treatment of inflammatory bowel disease (IBD)*
<235 pmol 6-TGN/8×108 red blood cells
235−450 pmol 6-TGN/8×108 red blood cells
Increasing risk for myelotoxicity and leucopenia
>450 pmol 6-TGN/8×108 red blood cells
>5700 pmol 6-MMPN/8×108 red blood cells
1 mL (Note: This volume does not allow for repeat testing.)
Collect blood in lavender-top (EDTA) tube only. Gently invert to mix. Submit whole blood refrigerated. Do not separate specimen. Do not freeze.
Refrigerate; stable refrigerated for 14 days. Stable at room temperature for one day. Unstable frozen.
Causes for Rejection
Frozen specimen; specimen not EDTA whole blood; gross hemolysis