title: Pre-analytic and analytic sources of variations in thiopurine methyltransferase activity measurement in patients prescribed thiopurine-based drugs: A systematic review.
abstract: OBJECTIVE
  Low thiopurine S-methyltransferase (TPMT) enzyme activity is associated with increased thiopurine drug toxicity, particularly myelotoxicity. Pre-analytic and analytic variables for TPMT genotype and phenotype (enzyme activity) testing were reviewed.
  
  
  METHODS
  A systematic literature review was performed, and diagnostic laboratories were surveyed.
  
  
  RESULTS
  Thirty-five studies reported relevant data for pre-analytic variables (patient age, gender, race, hematocrit, co-morbidity, co-administered drugs and specimen stability) and thirty-three for analytic variables (accuracy, reproducibility). TPMT is stable in blood when stored for up to 7 days at room temperature, and 3 months at -30°C. Pre-analytic patient variables do not affect TPMT activity. Fifteen drugs studied to date exerted no clinically significant effects in vivo. Enzymatic assay is the preferred technique. Radiochemical and HPLC techniques had intra- and inter-assay coefficients of variation (CVs) below 10%.
  
  
  CONCLUSIONS
  TPMT is a stable enzyme, and its assay is not affected by age, gender, race or co-morbidity.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Evelin
authors.initials: E
authors.lastname: Loit
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Tricco
authors.forename: Sophia
authors.initials: S
authors.lastname: Tsouros
authors.forename: Margaret
authors.initials: M
authors.lastname: Sears
authors.forename: Mohammed T
authors.initials: MT
authors.lastname: Ansari
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Booth
mesh_terms: D000375:Aging / Q000187:drug effects; D001379:Azathioprine / Q000009:adverse effects / Q000494:pharmacology*; D004795:Enzyme Stability / Q000187:drug effects; D019538:Health Care Surveys; D006400:Hematocrit; D006801:Humans; D015122:Mercaptopurine / Q000009:adverse effects / Q000494:pharmacology*; D008780:Methyltransferases / Q000032:analysis / Q000378:metabolism*; D055553:Prescription Drugs / Q000009:adverse effects / Q000494:pharmacology*; D011687:Purines / Q000009:adverse effects / Q000494:pharmacology*; D012727:Sex Characteristics; D013866:Thioguanine / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D055553:Prescription Drugs; D011687:Purines; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine