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HelpTest Code THIO Thiopurine Metabolites, Whole Blood
Ordering Guidance
This specimen cannot be shared with testing for tacrolimus, cyclosporine, sirolimus or everolimus. Testing for these must be ordered separately and separate specimens submitted.
Shipping Instructions
Specimen must be shipped refrigerated.
Specimen Required
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot, centrifuge, or freeze.
Secondary ID
65381Useful For
Aids physicians in dose adjustments, minimizing dose-dependent toxicity, and monitoring compliance of thiopurine drug therapy
Testing Algorithm
A red blood cell (RBC) count is performed followed by determination of thiopurine metabolite values by liquid chromatography tandem mass spectrometry. Values are utilized to calculate and report the final results (unit of measure: pmol/8 x 10[8] RBC) for 6-thioguanine nucleotides and 6-methylmercaptopurine derivative analyte.
For more information see:
-Ulcerative Colitis and Crohn Disease Therapeutic Drug Monitoring Algorithm
-TPMT Testing in the Treatment of Inflammatory Bowel Disease Algorithm
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name
Thiopurine Metabolites, BSpecimen Type
Whole Blood EDTASpecimen Minimum Volume
1.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole Blood EDTA | Refrigerated (preferred) | 8 days | |
| Ambient | 24 hours |
Reject Due To
| Gross hemolysis | Reject |
| Moderate hemolysis | Reject |
| Gross lipemia | OK |
| Gross icterus | OK |
| Clotted | Reject |
Clinical Information
This test is primarily used to verify compliance, optimize therapy, and identify elevated metabolite concentrations that may result in toxicity after initiation of thiopurine drug therapy for the treatment of inflammatory bowel disease. Recommended time points for monitoring include: 4 weeks after starting treatment to verify patient compliance and look for early risk of toxicity; 12 to 16 weeks after starting therapy when 6-thioguanine nucleotides have reached steady-state; and annually.(1) It may also be ordered in patients who do not respond to therapy as expected or as needed for dose changes, flare-ups, signs of toxicity, or suspicion of noncompliance. The test will measure 6-methylmercaptopurine and 6-thioguanine nucleotides in erythrocytes.
Reference Values
6-Thioguanine Nucleotides (6-TGN): 235-450 pmol/8x10(8) red blood cell (RBC)
6-Methylmercaptopurine (6-MMP): Less than or equal to 5700 pmol/8x10(8) RBC
Interpretation
Target 6-thioguanine concentrations are 235 to 450 pmol/8x10(8) red blood cell (RBC) with lower levels suggesting suboptimal dosing and higher levels associated with increased risk of myelotoxicity and leukopenia. High 6-methylmercaptopurine levels (greater than 5700 pmol/8x10[8] RBC) suggest an increased risk for hepatotoxicity and potentially "thiopurine hypermethylation."
Cautions
This test cannot be used to predict optimal starting dose. It is sensitive to hemolysis and transport conditions. This test does not replace monitoring of patients using other laboratory tests (eg, complete blood cell count, liver function tests).
Final concentrations are reported per the red blood cell (RBC) count (unit of measure =pmol/8 x 10[8] RBC) for the 6-thioguanine nucleotides and 6-methylmercaptopurine derivative analytes. Therefore, any significant lysis of the RBCs will lead to an artificially lower RBC count that could falsely increase the final concentrations. Due to this, moderately hemolyzed samples are rejected.
Clinical Reference
1. Goel RM, Blaker P, Mentzer A, Fong SCM, Marinaki AM, Sanderson JD. Optimizing the use of thiopurines in inflammatory bowel disease. Ther Adv Chronic Dis. 2015;6(3):138-146
2. Shipkova M, Armstrong VM, Wieland E, Oellerich M. Differences in nucleotide hydrolysis contribute to the differences between erythrocyte 6-thioguanine nucleotide concentrations determined by two widely used methods. Clin Chem. 2003:49(2):260-268
3. Boulieu R, Dervieux T. High-performance liquid chromatographic determination of methyl 6-mercaptopurine nucleotides (Me6-MPN) in red blood cells: analysis of Me6-MPN per se or Me6-MPN derivative? J Chromatogr B Biomed Sci Appl. 1999;730(2):273-276
4. Kirchherr H, Shipkova M, von Ahsen N. Improved method for therapeutic drug monitoring of 6-thioguanine nucleotides and 6-methylmercaptopurine in whole-blood by LC/MSMS using isotope-labeled internal standards. Ther Drug Monit. 2013:35(3):313-321
Method Description
Red blood cell count is first performed and then the thiopurine metabolites values are determined by mass spectrometry.(Unpublished Mayo Method)
Day(s) Performed
Monday, Wednesday, Friday
Report Available
2 to 4 daysSpecimen Retention Time
14 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
80299LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| THIO | Thiopurine Metabolites, B | 82869-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 49580 | 6-Thioguanine Nucleotides | 32660-3 |
| 49581 | 6-Methylmercaptopurine | 32654-6 |
Forms
If not ordering electronically, complete, print, and send Gastroenterology and Hepatology Test Request (T728) with the specimen