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Test Code LAB20141 Leflunomide Metabolite (Teriflunomide), Serum

Reporting Name

Leflunomide Metabolite, S
Covenant HealthCare Laboratory Test Directory Note:


Useful For

Therapeutic monitoring of patients actively taking leflunomide


Assessment of elimination in patients requiring enhanced elimination of the drug

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Serum Red

Specimen Required

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

1. Draw blood no sooner than 12 hours (trough value) after last dose.

2. Centrifuge within 2 hours of collection and aliquot serum into plastic vial.

Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Ambient (preferred) 28 days
  Frozen  28 days
  Refrigerated  28 days

Reference Values

Therapeutic: >40 mcg/mL

Elimination: <0.020 mcg/mL

Day(s) Performed

Monday, Wednesday, Friday

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
LEFLU Leflunomide Metabolite, S 44828-2


Result ID Test Result Name Result LOINC Value
60292 Leflunomide Metabolite, S 44828-2

Clinical Information

Leflunomide is a disease-modifying antirheumatic drug approved for therapy of rheumatoid arthritis and used off-label to reduce viral nephritis in renal transplant. It is a prodrug: rapid and complete metabolism converts leflunomide to its active metabolite, teriflunomide (also called A77 1726), which acts by inhibiting pyrimidine synthesis. Teriflunomide has a very long half-life, greater than 2 weeks on average.


There is marked interindividual variability in leflunomide pharmacokinetics, thus therapeutic monitoring of serum teriflunomide concentrations may be helpful in optimizing therapy. Therapeutic targets remain only loosely defined and appear to vary depending on the purpose of therapy, but serum teriflunomide concentrations greater than 40 mcg/mL have been associated with better clinical outcomes. Due to the long half-life, serum specimens for therapeutic monitoring may be drawn at any point in the dosing cycle, although trough (immediately before next schedule dose) sampling is preferred for consistency. Adverse reactions to leflunomide do not correlate well with serum drug concentration, but include diarrhea, hypertension, and liver toxicity.


Enhanced elimination of the drug may be required in patients who are or who wish to become pregnant, or who are experiencing toxicity; teriflunomide can persist up to 2 years after ceasing therapy unless elimination is accelerated. This can be accomplished through use of activated charcoal or a bile acid sequestrant such as cholestyramine, reducing the half-life of teriflunomide to approximately 1 day. Serum concentrations less than 0.020 mcg/mL (<20 ng/mL) on 2 independent tests at least 2 weeks apart are preferred for patients anticipating pregnancy to minimize the potential risk of teratogenesis associated with the drug.


Therapy: clinical targets for serum teriflunomide (leflunomide metabolite) concentrations are still being determined, but levels greater than 40 mcg/mL appear to correlate with better outcome.


Elimination: serum concentrations less than 0.020 mcg/mL (20 ng/mL) are preferred to minimize potential teratogenesis for patients considering pregnancy.

Method Description

Serum samples are diluted in an aqueous solution containing deuterated teriflunomide as an internal standard. This is injected onto a liquid chromatography system with Cohesive turboflow to separate the drug from serum components, and analyzed by negative-ion mode tandem mass spectrometry.(Unpublished Mayo method)

Report Available

3 to 5 days

Reject Due To

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Method Name

High-Turbulence Liquid Chromatography Mass Spectrometry (HTLC-MS/MS)


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