Test Catalog

Test ID: THIO    
Thiopurine Metabolites, Whole Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

Aids physicians in dose adjustments, minimizing dose-dependent toxicity, and monitoring compliance of thiopurine drug therapy

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Red blood cell (RBC) count is first performed and then the thiopurine metabolites' values are determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Values are utilized to calculate and report a final result (unit of measure: pmol/8 x 10[8] RBC) for 6-thioguanine nucleotides and 6-methylmercaptopurine derivative analyte.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 (6-MMP) and 6-thioguanine nucleotides (6-TGN) in erythrocytes.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

6-Thioguanine Nucleotides (6-TGN): 235-450 pmol/8x10(8) RBC

6-Methylmercaptopurine (6-MMP): Less than or equal to 5700 pmol/8x10(8) RBC

Interpretation Provides information to assist in interpretation of the test results

Target 6-thioguanine (6-TGN) concentrations are 235 to 450 pmol/8x10(8) RBC with lower levels suggesting suboptimal dosing and higher levels associated with increased risk of myelotoxicity and leukopenia. High 6-methylmercaptopurine (6-MMP) levels (greater than 5700 pmol/8x10[8] RBC) suggest an increased risk for hepatotoxicity and potentially "thiopurine hypermethylation."

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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 (ie, CBC, liver function tests).

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Goel RM, Blaker P, Mentzer A, et al: Optimizing the use of thiopurines in inflammatory bowel disease. Ther Adv Chronic Dis. 2015;6(3):138-146

2. Shipkova M, Armstrong V, 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. 1999:730:273-274

4. Kirchherr H, Shipkova M, 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