Methadone and Metabolite, Quantitative LC-MS/MS, Urine

Methadone and Metabolite, Quantitative LC-MS/MS, Urine
Start Date
Expiration Date
Amidone; Dolophine; EDDP; Heptadon; Methadone; Methadose; Physeptone; Symoron
CPT Codes
Reference Test
ATLAS Test Code

Specimen Information


Urine, random


4.0 ml

Transport Info

Room Temperature. Refrigerated acceptable.

Fasting Required?
Patient Instructions

Reference Range

Negative (less than assay limit of detection)


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

Clinical Significance

Confirm positive screen results by an alternate, specific method; detect use. Methadone is a synthetic diphenylheptane-derivative opiate agonist that was first synthesized by German chemists during World War II. The drug, available as methadone hydrochloride, occurs as colorless crystals or a white crystalline powder and is soluble in water and alcohol. In the U.S., methadone may be prescribed to relieve severe chronic pain, in terminally ill patients for example, and is administered orally or by parenteral injection. Methadone is also used as an oral substitute for heroin or other morphine-like drugs to suppress withdrawal symptoms and/or to temporarily maintain chronic relapsing heroin addicts. Methadone is classified as a Schedule II drug under the Federal Controlled Substances Act of 1970 and is subject to U.S. Food and Drug Administration regulations for drugs that require special studies, records, and reports when used for detoxification and maintenance of opiate dependence.The pharmacological activity of methadone is very similar to that of morphine, but differs in that it yields reliable effects when administered orally. Its overall abuse potential is comparable to that of morphine.Methadone is well absorbed from the gastrointestinal tract and can be detected in plasma within 30 minutes after oral ingestion. Peak concentrations are reached at about 4 hours after administration. It binds highly to tissue protein, resulting in its cumulative effects and slow elimination. Methadone undergoes extensive biotransformation in the liver. The major metabolites, the result of N-demethylation and cyclization, are excreted in the urine and the bile along with unchanged drug. These major metabolites are 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3, 3-diphenylpyrroline (EMDP). In patients on methadone maintenance, unchanged methadone may account for 5-50% of the dose and EDDP 3-25% of the dose excreted in urine during the first 24 hours. The amount of unchanged methadone excreted in the urine is dependent on urine pH, urine volume, dose administered, and rate of metabolism. The half life of methadone is 15-55 hours depending on the pH of the urine. A positive result indicates exposure to drug and does not necessarily indicate impairment.