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HelpMayo Test ID MDNS Methadone and Metabolites, Serum
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.
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, SSpecimen Type
Serum RedSpecimen 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 daysPerforming 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. It has not been cleared or approved by the US Food and Drug Administration.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 |