Journal
JOURNAL OF APPLIED LABORATORY MEDICINE
Volume 4, Issue 1, Pages 40-49Publisher
AMER ASSOC CLINICAL CHEMISTRY
DOI: 10.1373/jalm.2018.027730
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Objective: Methotrexate (MTX) polyglutamate (MTXPG(3)) levels from isolated red blood cells (RBCs) collected by venipuncture have clinical utility in guiding MTX dosing for patients with rheumatoid arthritis (RA). Our objective was to transition this RBC-based therapeutic drug monitoring (TDM) assay to dried capillary blood collected by fingerstick. Methods: Patients with RA treated with MTX were enrolled. Specimens were collected by fingerstick (volumetric absorptive microsampler) and venipuncture to measure MTXPG(3) from dried capillary blood, total venous blood, and isolated RBCs. MTXPG(3) levels from dried capillary blood were measured using LC-MS/MS, converted to RBC equivalent (nmol/L), and compared with those from isolated RBCs (reference method). Following transition to fingerstick collection, comparability in the distributions of dried capillary and venipuncture-based RBC MTXPG(3) levels was assessed using the Kolmogorov-Smirnov (K-S) test. Results: Intraday and interday precision ranged from 2.0% to 10.9% and 3.1% to 10.8%, respectively, at MTXPG(3) concentrations ranging from 5 to 100 nmol/L. In 106 participants treated with MTX, MTXPG3 levels from total venous and dried capillary blood were comparable [slope = 0.97 (95% CI, 0.92-1.03); R-2 = 0.92]. Dried capillary blood MTXPG(3) converted to RBC equivalent was similar to levels from isolated RBCs(30 +/- 18 nmol/L vs 33 +/- 19 nmol/L; n = 106). After implementation in the clinical laboratory, RBC equivalents MTXPG(3) from the fingerstick method were similar to levels from venipuncture [39 +/- 22 nmol/L (n = 825) vs 39 +/- 24 nmol/L (n = 47935)] (K-S test P = 0.09). Underexposure to MTX (MTXPG(3) <= 5 nmol/L RBCs) was detected in 7.0% and 8.5% patient specimens collected using the fingerstick and venipuncture methods, respectively. Conclusion: Capillary blood MTXPG3 levels can be used to guide MTX dosing in TDM practice.
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