Thiopurine Metabolites

CPT: 80299
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Test Details

Synonyms

  • 6MP Metabolites
  • 6TG Metabolites
  • Azathioprine Metabolites
  • Mercaptopurine Metabolites

Use

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.

Limitations

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.

Methodology

Whole blood washing and red blood cell harvesting/counting. Liquid chromatography/tandem mass spectrometry (LC/MS-MS) after acidic hydrolysis.

Reference Interval

See table.

*Chevaux JB, Peyrin-Biroulet L, Sparrow MP. Optimizing thiopurine therapy in inflammatory bowel disease. Inflamm Bowel Dis. 2011 Jun; 17(6):1428-1435.

6-TGN

For treatment of inflammatory bowel disease (IBD)*

Suboptimal dosing

<235 pmol 6-TGN/8×108 red blood cells

Optimal dosing

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

6-MMPN

Hepatotoxicity risk

>5700 pmol 6-MMPN/8×108 red blood cells

Specimen Requirements

Specimen

Whole blood

Volume

3 mL

Minimum Volume

1 mL (Note: This volume does not allow for repeat testing.)

Container

Lavender-top (EDTA) tube

Collection

Collect blood in lavender-top (EDTA) tube only. Gently invert to mix. Submit whole blood refrigerated. Do not separate specimen. Do not freeze.

Storage Instructions

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

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
503800 Thiopurine Metabolites 503804 6-TGN pmol/8x 10E8 32660-3
503800 Thiopurine Metabolites 503806 6-MMPN pmol/8x 10E8 32654-6
503800 Thiopurine Metabolites 503807 Thiopurine Metabolites N/A
Reflex Table for 6-MMPN
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 000000 Serial Monitoring 000000 Serial Monitoring N/A

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