Transition of Methotrexate Polyglutamate Drug Monitoring Assay from Venipuncture to Capillary Blood-Based Collection Method in Rheumatic Diseases.

Abstract

OBJECTIVE:

Methotrexate (MTX) polyglutamate (MTXPG3) 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 MTXPG3 from dried capillary blood, total venous blood, and isolated RBCs. MTXPG3 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 MTXPG3 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 MTXPG3 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 MTXPG3 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 MTXPG3 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 (MTXPG3 ≤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.

• Authors: Kelley Brady, Ying Qu, Deborah Stimson, Robert Apilado, Roberta Vezza Alexander, Smitha Reddy, Puja Chitkara, John Conklin, Tyler O'Malley, Claudia Ibarra, Thierry Dervieux
• Journal: The journal of applied laboratory medicine (J Appl Lab Med) Vol. 4 Issue 1 Pg. 40-49 (07 2019) ISSN: 2576-9456 [Print] England
• PMID: 31639706 (Publication Type: Journal Article)
• Copyright: © 2018 American Association for Clinical Chemistry.

Chemical References

• Polyglutamic Acid
• methotrexate polyglutamate
• Methotrexate

Topics

• Blood Specimen Collection (methods)
• Chromatography, Liquid
• Drug Monitoring (methods)
• Erythrocyte Count
• Female
• Humans
• Male
• Methotrexate (analogs & derivatives, pharmacology)
• Middle Aged
• Phlebotomy
• Polyglutamic Acid (analogs & derivatives, pharmacology)
• Retrospective Studies
• Rheumatic Diseases (blood, drug therapy)
• Tandem Mass Spectrometry