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Test ID: MTXSG Methotrexate Post Glucarpidase, Serum

Reporting Name

Methotrexate Post Glucarpidase, S

Useful For

Monitoring methotrexate concentrations postglucarpidase therapy

Clinical Information

Methotrexate, an antimetabolite (folate reductase inhibitor), is used at high dose (12 gm/m[2]) to treat neoplastic diseases, such as lymphocytic leukemia. Therapy is guided by measurement of serum concentration: 24 hours after dosage, the serum concentration should be less than 10 mcmol/L; 48 hours after dosage, concentration should be less than 1 mcmol/L; and 72 hours after dosage, the concentration should be less than 0.1 mcmol/L or less than 0.05 mcmol/L, depending on clinical protocol. It is also administered at low dose (a single dose of 5-15 mg per week) to treat severe psoriasis and rheumatoid arthritis. Methotrexate is 65% orally bioavailable. Peak serum concentrations are reached 2 to 3 hours after dosing. Protein binding is approximately 45%. Volume of distribution is 0.4 L/kg. Elimination is concentration dependent with an apparent elimination half-life of 1.8 hours when the serum concentration is above 1 mcmol/L, 8 hours when between 0.1 and 1 mcmol/L, and approximately 30 hours when below 0.1 mcmol/L.


Voraxaze (glucarpidase) is a carboxypeptidase enzyme indicated for the treatment of toxic plasma methotrexate (MTX) concentrations (>1 mcmol/L) in patients with delayed methotrexate clearance due to impaired renal function. Measurement of methotrexate using immunoassays is unreliable for specimens collected within 48 hours following Voraxaze administration since it can result in falsely elevated results. As a result, this liquid chromatography-tandem mass spectrometry assay should be used to monitor MTX concentrations postglucarpidase therapy.


Following a 4 to 6 hour intravenous infusion of methotrexate, postinfusion concentrations greater than the following indicate an increased risk of toxicity if conventional low-dose leucovorin rescue is given:

-24-hour postinfusion concentration: 5.0 to 10.0 mcmol/L

-48-hour postinfusion concentration: 0.5 to 1.0 mcmol/L

-72-hour postinfusion concentration: 0.1 mcmol/L

Report Available

Same day/1 day

Day(s) Performed

Monday through Sunday

Clinical Reference

1. Cadman EC, Durivage HJ: Cancer chemotherapy: alkylating agents. In: Wilson JD, Braunwald E, Isselbacher KJ, eds. Harrison's Principles of Internal Medicine. 12th ed. McGraw-Hill Book Company; 1991: 1592-1594

2. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J, eds: Harrison's Principles of Internal Medicine. 20th ed. McGraw-Hill Education; 2018

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Specimen Type


Shipping Instructions

Ship specimen in amber vial to protect from light.

Specimen Required

Supplies: Amber Frosted Tube, 5 mL (T192)

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Amber vial

Specimen Volume: 1 mL

Specimen Minimum Volume

0.2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 7 days LIGHT PROTECTED
  Frozen  14 days LIGHT PROTECTED
  Ambient  7 days LIGHT PROTECTED

Reference Values

Nontoxic drug concentration after 72 hours: <0.1 mcmol/L

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
MTXSG Methotrexate Post Glucarpidase, S 51602-1


Result ID Test Result Name Result LOINC Value
62580 Methotrexate Post Glucarpidase, S 51602-1


If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.

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