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EPIC CODE: TRAM Tramadol and Metabolite, Random, Urine

Secondary ID


Useful For

Monitoring of compliance utilizing tramadol


Detection and confirmation of the illicit use of tramadol

Method Name

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

Reporting Name

Tramadol and Metabolite, U

Specimen Type


Ordering Guidance


Additional Testing Requirements

If urine creatinine is required or adulteration of the sample is suspected, the following test should also be ordered ADULT / Adulterants Survey, Random, Urine.

Specimen Required

Supplies: Sarstedt 5 mL Aliquot Tube (T914)

Collection Container/Tube: Plastic urine container

Submission Container/Tube: Plastic vial, 5 mL

Specimen Volume: 1 mL

Collection Instructions:

1. Collect a random urine specimen.

2. No preservative.

Additional Information:

1. No specimen substitutions.

2. STAT requests are not accepted for this test.

3. Submitting <1 mL will compromise our ability to perform all necessary testing.

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Urine Refrigerated (preferred) 14 days
  Ambient  14 days
  Frozen  14 days

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Tramadol, a centrally acting opioid analgesic, is utilized in the treatment of moderate to moderately severe pain. Tramadol acts as an opiate agonist through the binding of the parent drug and its O-desmethyl (M1) metabolite to mu-opioid receptors and through the weak inhibition of norepinephrine and serotonin reuptake. The active metabolite, O-desmethyltramadol, is a considerably more potent mu-opioid receptor agonist than its parent drug. In urine, approximately 30% of tramadol is excreted as unchanged drug, while approximately 60% is excreted as metabolites (N- and O-desmethyltramadol). The half-life of tramadol and O-desmethyltramadol is approximately 7 hours.

Reference Values

Cutoff: 25 ng/mL


The presence of tramadol or O-desmethyltramadol levels of 25 ng/mL or higher is a strong indicator that the patient has used tramadol.


Urine concentrations do not correlate well with serum drug levels and are not intended for therapeutic drug management.


Results are intended to be interpreted by a physician or health care professional. This test is not intended for use in employment-related testing.

Clinical Reference

1. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923

2. Dayer P, Collart L, Desmeules J: The pharmacology of tramadol. Drugs. 1994;47(Suppl 1):3-7

3. Langman LJ, Bechtel L, Meier BM, Holstege CP: Clinical toxicology. In: Rifai N, Horwath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:832-887

Day(s) Performed

Tuesday, Thursday

Report Available

2 to 6 days

Specimen Retention Time

14 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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


G0480 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
TRAM Tramadol and Metabolite, U 100734-3


Result ID Test Result Name Result LOINC Value
35914 Tramadol 17719-6
35915 O-desmethyltramadol 92639-4

NY State Approved


Method Description

Isotopically labeled tramadol and O-desmethyltramadol are added to the sample as internal standards. The sample is then diluted with deionized water and the analytes are separated by liquid chromatography and then quantified by mass spectrometry using multiple reaction monitoring.(Patel BN, Sharma N, Sanyal M, Shrivastav PS: An accurate, rapid and sensitive determination of tramadol and its active metabolite O-desmethyltramadol in human plasma by LC-MS/MS. J Pharm Biomed Anal. 2009 Feb 20;49[2]:354-366)


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