Test Id : MTDNU
Methadone Confirmation, Random, Urine
Useful For
Suggests clinical disorders or settings where the test may be helpful
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
A short description of the method used to perform the test
Gas Chromatography Mass Spectrometry (GC-MS) Confirmation with Quantitation
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Dolophine (Methadone)
Methadone (Dolophine)
EDDP
2-Ethylidene-1,5-Dimethyl-3,3-Diphenylpyrrolidine
Specimen Type
Describes the specimen type validated for testing
Urine
Ordering 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Supplies: Urine Tubes, 10 mL (T068)
Collection Container/Tube: Plastic urine container
Submission Container/Tube: Plastic, 10-mL urine tube
Specimen Volume: 10 mL
Collection Instructions:
1. Collect a random urine specimen.
2. No preservative.
Forms
If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
2.5 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | OK |
| Gross icterus | OK |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Urine | Refrigerated (preferred) | 28 days | |
| Ambient | 14 days | ||
| Frozen | 28 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
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
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Negative (Positive results are reported with a quantitative result.)
Cutoff concentrations by gas chromatography mass spectrometry:
METHADONE: 100 ng/mL
2-ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDINE (EDDP): 100 ng/mL
Interpretation
Provides information to assist in interpretation of the test results
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
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Gutstein HB, Akil H. Opioid analgesics. In: Hardman JG, Limbird LE, eds. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 10th ed. McGraw-Hill; 2001:569-619
2. Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet. 2002;41(14):1153-1193
3. Ferrari A, Coccia CP, Bertolini A, Sternieri E. Methadone-metabolism, pharmacokinetics and interactions. Pharmacol Res. 2004;50(6):551-559
4. Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 10th ed. Biomedical Publications; 2014
5. Levine B. Principles of Forensic Toxicology. 2nd ed. AACC Press; 2003:385
6. Galloway FR, Bellet NF. Methadone conversion to EDDP during GC-MS analysis of urine samples. J Anal Toxicol. 1999;23(7):615-619
7. George S, Braithwaite RA. A pilot study to determine the usefulness of the urinary excretion of methadone and its primary metabolite (EDDP) as potential markers of compliance in methadone detoxification programs. J Anal Toxicol. 1999;23(2):81-85
8. 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
Method Description
Describes how the test is performed and provides a method-specific reference
Confirmation testing is performed by gas chromatography mass spectrometry, solid phase extraction.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Tuesday, Thursday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
G0480
80358 (if appropriate for select payers)
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| MTDNU | Methadone Confirmation, U | 104626-7 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 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 |