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Drugs / Therapeutic MonitoringTier 2 · Mid-Specialty

METHADONE

Also known as: Methadone Serum · Methadone Drug Test · Methadone Level · Opioid Maintenance Test · EDDP Test

Sample: Serum Reference price: ₹200Code: ZNT-METHADONE

What this test measures

Methadone is a long-acting synthetic opioid used both as a treatment for chronic pain and, more commonly, as an opioid-substitution therapy (OST) for opioid use disorder. Its half-life is 24–36 hours, much longer than morphine or heroin, which lets a single daily dose suppress withdrawal and cravings. The test measures methadone and often its main metabolite EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), which confirms actual metabolism rather than someone simply adding methadone to a urine sample.

Methadone is not routinely detected by standard opiate immunoassays — those target morphine-codeine-like opioids. A specific methadone assay is needed, and confirmation is by LC-MS/MS.

Why it matters

In India, methadone OST programmes run under the AIIMS National Drug Dependence Treatment Centre and ICMR-supported clinics, particularly in states with high heroin use (Punjab, Manipur, Mizoram). Confirming methadone presence and concentration matters in three settings: (1) verifying adherence in OST patients (a positive test = patient is taking the prescribed dose), (2) emergency assessment of opioid overdose (methadone overdose is dangerous because of its long half-life and QT-interval prolongation), and (3) pain-clinic monitoring of chronic-pain patients on prescribed methadone.

Methadone causes more drug-induced cardiac arrhythmias and overdose deaths than most opioids because of its narrow safety margin, slow metabolism, and major drug interactions (especially with QT-prolonging drugs and CYP3A4 inhibitors).

How to prepare

For OST adherence monitoring the sample is usually drawn at the clinic just before the next supervised dose (trough). For overdose evaluation, the sample is drawn on presentation — the timing relative to last dose is recorded. No fasting needed. Tell the lab and the clinic about all other medications, including herbal preparations, because many alter methadone metabolism.

Markers & reference ranges

Reference ranges below are typical adult values. Your lab's reported range may differ slightly based on the assay platform and patient demographics — always read your report against the range printed on it.

MarkerNormal rangeIf lowIf high
Methadone (ng/mL)[1][2][3]Therapeutic 100 – 400 ng/mL (OST trough)Not detected: no recent intake — relapse, missed dose, or non-adherence. < 100 ng/mL on a trough sample: usually sub-therapeutic; dose review needed.400 – 1000 ng/mL: high end of therapeutic; watch for sedation. > 1000 ng/mL: toxic range; risk of respiratory depression and prolonged QT. Always interpret with the EDDP metabolite — methadone present but no EDDP suggests sample tampering rather than actual intake.

Methadone serum interpretation

Range (ng/mL)CategoryClinical context
Not detectedNegativeNo recent intake; possible non-adherence in OST patient
100 – 400Therapeutic (trough)OST or chronic-pain dosing within target
400 – 1000High therapeuticMay reflect recent peak or higher prescribed dose
> 1000ToxicRisk of sedation, respiratory depression, QT prolongation

Frequently asked questions

Why is methadone not picked up on a routine drug screen?

Standard opiate immunoassays target morphine and codeine-like opioids. Methadone has a different chemical structure and needs a specific methadone test. Ask for a methadone-specific assay (with EDDP) if it is relevant.

What is EDDP and why does it matter?

EDDP is the main metabolite of methadone. Its presence confirms that methadone has been ingested and metabolised — not just added to the sample to fake a result. Reputable adherence-monitoring panels report both.

How long is methadone detectable?

In blood, methadone is detectable for 2–4 days after the last dose. In urine, up to 7–10 days, especially in long-term users.

Why is methadone overdose more dangerous than heroin?

Methadone has a much longer half-life (24–36 hours vs heroin's ~30 minutes). After overdose, breathing depression can come back hours after the initial naloxone reversal because methadone keeps releasing from tissues. Methadone also prolongs the QT interval and can trigger fatal arrhythmias.

Is methadone legal in India?

Yes, but only under regulated programmes for opioid-substitution therapy and chronic pain. AIIMS, ICMR-supported centres, and licensed pain clinics dispense it under strict supervision. Personal possession without prescription is illegal.

Can other drugs interfere with methadone levels?

Yes. CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, efavirenz) lower methadone levels and can trigger withdrawal. CYP3A4 inhibitors (some antifungals, certain antibiotics, grapefruit juice) raise levels and increase overdose risk. Always tell your doctor every medicine, herbal product, or recreational drug you take.

Why is QT-interval monitoring important on methadone?

High doses of methadone (especially > 100 mg/day) prolong the QT interval on ECG and rarely cause torsades de pointes — a dangerous arrhythmia. Most guidelines recommend a baseline ECG and repeat at 1 month and yearly thereafter, or sooner if other QT drugs are added.

Related Drugs / Therapeutic Monitoring tests

Tests commonly ordered alongside METHADONE, or that help interpret an unexpected result.

Sources & references

  1. NCBI StatPearls — Methadone · accessed 2026-05-30T00:00:00.000Z
  2. NIH NIDA — Methadone (Medications for Opioid Use Disorder) · accessed 2026-05-30T00:00:00.000Z
  3. Mayo Clinic Labs — Methadone, Serum · accessed 2026-05-30T00:00:00.000Z
  4. FDA — Methadone Prescribing Information · accessed 2026-05-30T00:00:00.000Z

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