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Test Code MDNS Methadone and Metabolites, Serum

Useful For

Compliance monitoring of methadone

 

Assessment of methadone toxicity

Method Name

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

Reporting Name

Methadone and Metabolite, S

Specimen Type

Serum Red


Specimen Required


Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Container/Tube: Red top (Serum gel/SST are not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 1.0 mL

Collection Instructions: Within 2 hours of collection, centrifuge and aliquot serum into a plastic vial.


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  14 days

Reject Due To

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Clinical Information

Methadone, a long-acting synthetic opioid analgesic, is an agonist at the mu receptor. It has several actions qualitatively similar to those of morphine, primarily involving the central nervous system and organs composed of smooth muscles. Analgesia, sedation, and detoxification or maintenance in opioid addiction can be achieved with therapeutic use of methadone hydrochloride. Methadone acts by binding to the mu-opioid receptor but also has some affinity for the N-methyl-D-aspartate receptor (NMDA) ionotropic glutamate receptor.

 

Methadone undergoes extensive biotransformation in the liver. Methadone is metabolized by cytochrome P450 (CYP) 3A4, CYP2B6, CYP2C19, and CYP2D6 enzymes. It is also a substrate for the P-glycoprotein efflux protein. The major inactive metabolite is a result of N-demethylation and cyclization, and forms 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP).

 

Substantial interindividual and intraindividual variabilities in metabolism and elimination have been noted. The half-life of methadone is highly variable and typically ranges from 7 to 59 hours; however, longer half-lives have been reported.

Reference Values

Not established

Interpretation

There is a significant overlap between the reported therapeutic and toxic concentrations of methadone in blood specimens.

Cautions

Methadone has a wide therapeutic index and dose-dependent toxicity. As a result, routine drug monitoring is not indicated in all patients.

 

Specimens collected in serum gel tubes are not acceptable because the drug can absorb on the gel and lead to falsely decreased concentrations.

Clinical Reference

1. Langman LJ, Bechtel LK, Holstege CP. Clinical toxicology. In: Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023:chap 43

2. Yaksh TL, Wallace MS. Opioids, analgesia, and pain management. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill Book Company; 2011:chap 18

3. Baselt RC. Disposition of Toxic Drugs and Chemical in Man. 9th ed. Biomedical Publications; 2011:1021-1025

Method Description

Liquid/liquid extraction of the serum sample followed by liquid chromatography tandem mass spectrometry.(Unpublished Mayo method)

Day(s) Performed

Tuesday, Thursday

Report Available

3 to 5 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

CPT Code Information

80299

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MDNS Methadone and Metabolite, S 96602-8

 

Result ID Test Result Name Result LOINC Value
36309 Methadone 3772-1
36310 EDDP 60071-8

Test Classification

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

Forms

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

Secondary ID

36309

Specimen Retention Time

14 days