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HelpTest Code MTDNU Methadone Confirmation, Random, Urine
Reporting Name
Methadone Confirmation, UUseful For
Monitoring for compliance of methadone treatment for analgesia or drug rehabilitation
Assessing compliance with rehabilitation programs by urine measurement of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
Method Name
Gas Chromatography Mass Spectrometry (GC-MS) Confirmation with Quantitation
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
UrineOrdering Guidance
1. For situations where chain of custody is required, a Chain-of-Custody Kit (T282) is available. For chain-of-custody testing, order MTDNX / Methadone Confirmation, Chain of Custody, Random, Urine.
2. Additional drug panels and specific requests are available. Call 800-533-1710 or 507-266-5700.
3. If urine creatinine is required or adulteration of the sample is suspected, order ADULT / Adulterants Survey, Random, Urine.
Specimen Required
Supplies: Urine Tubes, 10 mL (T068)
Container/Tube: Plastic, 10-mL urine tube
Specimen Volume: 10 mL
Collection Instructions:
1. Collect a random urine specimen.
2. No preservative.
Specimen Minimum Volume
2.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Urine | Refrigerated (preferred) | 28 days | |
| Frozen | 28 days | ||
| Ambient | 14 days |
Reject Due To
| Gross hemolysis | OK |
| Gross icterus | OK |
Reference Values
Negative
Cutoff concentrations:
METHADONE BY GC-MS
<100 ng/mL
2-ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDINE GC-MS
<100 ng/mL
Day(s) Performed
Tuesday, Thursday
CPT Code Information
80358
G0480 (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MTDNU | Methadone Confirmation, U | 104626-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 56028 | EDDP-by GC-MS | 104627-5 |
| 83129 | Methadone-by GC-MS | 104628-3 |
| 21107 | Methadone Interpretation | 69050-3 |
| 21110 | Chain of Custody | 77202-0 |
Clinical Information
Methadone (Dolophine) is a synthetic opioid, a compound that is structurally unrelated to natural opiates but is capable of binding to opioid receptors. These receptor interactions create many of the same effects seen with natural opiates including analgesia and sedation. However, methadone does not produce feelings of euphoria and has substantially fewer withdrawal symptoms than opiates such as heroin.(1) Methadone is used clinically to relieve pain, treat opioid abstinence syndrome, and treat heroin addiction in an attempt to wean patients from illicit drug use.
Metabolism of methadone to inactive forms is the main form of elimination. Oral delivery of methadone makes it subject to first-pass metabolism by the liver and creates interindividual variability in its bioavailability, which ranges from 80% to 95%. The most important enzymes in methadone metabolism are cytochrome P450 (CYP) 3A4 and CYP2B6.(1-4) CYP2D6 appears to have a minor role, and CYP1A2 may possibly be involved.(1-5) Methadone is metabolized to a variety of metabolites with the primary metabolite being 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP).(1-4) The efficiency of this process is prone to wide inter- and intraindividual variability, due to inherent differences in enzymatic activity as well as enzyme induction or inhibition by numerous drugs. Excretion of methadone and its metabolites (including EDDP) occurs primarily through the kidneys.(1,4)
Patients who are taking methadone for therapeutic purposes excrete both parent methadone and EDDP in their urine. Clinically, it is important to measure levels of both methadone and EDDP. Methadone levels in urine vary widely depending on factors such as dose, metabolism, and urine pH.(5) EDDP levels, in contrast, are relatively unaffected by the influence of pH and are, therefore, preferable for assessing compliance with therapy.(5)
Some patients undergoing treatment with methadone have attempted to pass compliance testing by adding a portion of the supplied methadone to the urine.(6) This is commonly referred to as "spiking.'' In these situations the specimen will contain large amounts of methadone and no or very small amounts of EDDP.(6) The absence of EDDP in the presence of methadone in urine strongly suggests adulteration of the urine specimen by direct addition of methadone to the specimen.
Interpretation
The absolute concentration of methadone and its metabolites found in patient urine specimens can be highly variable and does not correlate with dose. However, the medical literature and our experience show that patients who are known to be compliant with their methadone therapy have ratios of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP):methadone of greater than 0.60.(7)
An EDDP:methadone ratio less than 0.090 strongly suggests manipulation of the urine specimen by direct addition of methadone to the specimen.(6)
Cautions
Urine pH has a considerable effect on the ability to detect methadone, thus 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine is preferable for urine measurements.
Urine concentrations of methadone show very poor correlation to serum levels or the amount of drug administered.
Method Description
Confirmation testing is performed by gas chromatography mass spectrometry, solid phase extraction.(Unpublished Mayo method)