(RS)-methadone
Enable an AI agent to recognise racemic methadone, assess the identity and condition of a represented material, and determine which handling or referral actions its evidence and authorisations support.
Research draft, second pass
A second pass drafted this model: the structure a model of this thing needs, and what is known about it in the world. The line under this one says how the second half was obtained - researched against sources, or recalled without web access, in which case nothing here was read anywhere and every claim is a lead to verify. Unreviewed either way.
Researched by: Codex + Grok
Purpose and description
Enable an AI agent to recognise racemic methadone, assess the identity and condition of a represented material, and determine which handling or referral actions its evidence and authorisations support.
(RS)-methadone is the racemic 1:1 mixture of the (R)- and (S)-enantiomers of 6-(dimethylamino)-4,4-diphenylheptan-3-one, a synthetic diphenylheptane µ-opioid receptor agonist used clinically almost always as the hydrochloride salt for opioid agonist therapy and as a long-acting analgesic.
It can be Reconcile an incoming methadone label with chemical identity and stereochemical evidence.; Request qualified identity, chiral-composition or impurity testing where evidence is insufficient.; Compare methadone contents only after resolving chemical form and quantity basis.; Flag or quarantine material with conflicting identity, failed specifications or unresolved storage excursions.; Route a proposed transfer, use or disposal through the applicable material and authorisation checks..
Distinguishing features
Confirm methadone molecular connectivity against a suitable reference; the molecular formula C21H27NO alone cannot establish identity. Reference: [PubChem methadone](https://pubchem.ncbi.nlm.nih.gov/compound/Methadone).
Require evidence of an approximately equimolar R/S composition to verify the racemic designation; an unspecified stereochemical label does not establish that composition. Reference: [PubChem racemic methadone record](https://pubchem.ncbi.nlm.nih.gov/substance/178102108).
Distinguish a racemate from an isolated or enriched enantiomer using an enantioselective measurement with a stated acceptance criterion.
Resolve whether a material is the free base, a salt or a formulation before comparing identity records or quantities.
Distinguish identified methadone from a nonspecific opioid screening result by requiring a method capable of discriminating the candidate substances.
Scope
+ Methadone molecular identity and racemic stereochemical composition
+ Evidence distinguishing declared identity from analytically verified identity
+ Material form and the basis on which methadone quantity is expressed
+ Purity, contamination, storage history and fitness for a stated material use
+ Substance-specific handling constraints and links to applicable authorisations
- Patient diagnosis, treatment selection, dosing and clinical monitoring
- Finished medicinal product composition, packaging and marketing authorisation
- Independent models of isolated methadone enantiomers or other chemical substances
- Manufacturing processes and synthesis instructions
- Organisation-wide inventory, prescribing and controlled-substance compliance systems
Characteristics
- Identity confidence
- declared only | analytically supported | conflicting | unresolved Prevents a label or registry match from being treated as proof of the material's identity.
- R/S composition
- Mole fraction of each enantiomer, uncertainty and method-specific acceptance interval Determines whether the represented material supports the racemic designation.
- Chemical form
- free base | identified salt | form unresolved; record counterion and solvation where established Controls interpretation of analytical results and substance quantities.
- Methadone content
- mg/g, mg/mL or mol/L with explicit free-base or salt basis and uncertainty Supports valid comparisons without confusing material mass with methadone content.
- Impurity profile
- Identified and unidentified components with concentrations, reporting limits and methods Separates identity confirmation from suitability for the intended use.
- Material context
- Link to bulk lot, reference material, formulation or analytical sample Determines which specifications and evidence apply to the represented methadone.
- Condition assessment
- within documented conditions | excursion recorded | deterioration suspected | unknown Makes storage uncertainty visible before material is used or transferred.
- Action eligibility
- supported | restricted | pending evidence | prohibited under cited authority Connects a particular proposed action to material fitness and current permissions.
Also called
Where this came from
wikidata · CC0 1.0
Drafted structure
Bundle to layer to finding to question, as the second pass will find it: 6 bundles · 11 layers · 18 findings · 37 questions.
Methadone identity Establish whether the represented material supports the registered racemic methadone identity.
A methadone name match cannot distinguish molecular identity, stereochemical composition and an unsupported declaration.
Molecular identification
Connect the registry identity to discriminating chemical evidence.
Methadone connectivity evidence
Record the reference identity, test evidence and competing identities excluded by that evidence.
- Which structural reference defines methadone for this entry? definition
- Which analytical evidence distinguishes methadone from plausible alternative substances in this material? measurement
- Does the available result establish methadone identity or only membership in a broader screening category? boundary
Racemic composition
Evaluate the R/S composition independently of total methadone identification.
Racemate verification
Record whether the racemic designation is declared or measured, including the acceptance basis.
- What R and S mole fractions were measured, with what uncertainty? measurement
- Which enantioselective method and reference materials support those assignments? provenance
- What supported tolerance distinguishes an acceptable racemate from enantiomer-enriched material? boundary
Chemical form and content Resolve how methadone is physically represented and quantified.
Free-base, salt and formulation quantities cannot be compared without an explicit chemical and measurement basis.
Form resolution
Identify the chemical form and its relationship to the registry entry.
Base, salt and matrix
Record free-base or salt identity separately from any solvent, excipient or sample matrix.
- Is the methadone represented as free base or an identified salt, and what evidence establishes this? definition
- Which counterion, solvation state or matrix components affect interpretation of the material? measurement
- Does the registry treat this form as a representation of this entry or as a related registered thing? boundary
Quantity interpretation
Make methadone content comparable across supported material representations.
Content basis
Attach quantity basis, method and uncertainty to each content claim.
- Is the reported amount expressed as methadone free-base equivalent, a specified salt or total material? definition
- What assay or concentration result applies to this sample, and on what moisture or solvent basis? measurement
- Are chemical form and composition sufficiently established to support the proposed quantity conversion? action
Analytical quality and condition Assess whether identified racemic methadone meets the requirements of a stated material use.
Correct identity does not establish acceptable impurity levels or continued fitness after storage.
Purity and contamination
Evaluate methadone content and non-methadone components against an applicable specification.
Use-specific quality
Record which quality requirements have actually been tested and satisfied.
- Which specification applies to this material's intended laboratory or pharmaceutical use? boundary
- Which impurities, residual solvents or contaminants were measured, and what remained below or outside the method's reporting capability? measurement
- Do the reported results justify acceptance, rejection or further testing under that specification? action
Storage and stability
Assess condition using evidence applicable to the actual methadone form and container.
Condition validity
Connect storage history, observed changes and retest status to a defensible condition assessment.
- Which documented storage conditions and expiry or retest provisions apply to this form and container? provenance
- What excursions, container failures or physical changes have been recorded since the last accepted assessment? measurement
- What evidence is required before material affected by an excursion can return to its intended use? action
Lot and evidence linkage Ensure identity and quality claims apply to the methadone material being assessed.
A certificate for another lot or a methadone assay without chiral analysis cannot establish this material's racemic identity and quality.
Sample-to-lot link
Connect the assessed material with the sample and lot represented by its evidence.
Representative evidence
Record traceable sample identity and the limits of applying its results to the represented material.
- Which lot, container and sampled portion does each methadone identity or composition result represent? provenance
- Have subdivision, mixing, dilution or repackaging changed the applicability of the original results? boundary
Claim coverage
Separate the evidence supporting molecular identity, racemic composition, content and quality.
Certificate coverage and conflicts
Expose untested claims and contradictions between labels, certificates and measurements.
- Which documents or measurements support each of the methadone identity, R/S ratio, content and impurity claims? provenance
- Where do the label, certificate and independent results disagree or leave a claim unverified? boundary
- Which claim must remain unresolved until a qualified review or additional test settles the conflict? action
Hazards and permitted actions Connect substance hazards, material fitness and applicable permissions to a proposed action.
Methadone-related hazard information and controlled handling requirements need explicit context before an agent can support a material action.
Exposure context
Distinguish material-handling assessment from patient-specific clinical decisions.
Methadone hazard applicability
Record hazards and their evidence context. Methadone hydrochloride medicinal-product labeling identifies life-threatening respiratory depression and QT prolongation; handling decisions require information applicable to the actual material and exposure. Reference: [DailyMed methadone hydrochloride labeling](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d702d32b-98b1-412d-934c-1cd96af4b95a).
- Which safety information applies to this methadone form, concentration and proposed handling activity? provenance
- What exposure controls does the applicable safety assessment require for the proposed activity? action
- Does the proposed decision require referral to a clinical or emergency-response model? boundary
Action authorisation
Determine whether a specific action is supported in its jurisdiction and institutional setting.
Permitted material action
Record action-specific authorisation evidence separately from analytical fitness.
- Which current jurisdictional rules and institutional permissions govern the proposed possession, testing, transfer or disposal? provenance
- Are the proposed actor, recipient, purpose and material form covered by those permissions? boundary
- Should the agent support the action, hold the material pending evidence or refer the decision to the responsible authority? action
Evidence and external alignment What the world already says about this thing, gathered so the model can be checked against it.
A model that cannot be lined up against existing standards, identifiers and practice cannot be adopted by anyone who already uses them.
Reported evidence
Findings from the breadth pass, kept separate from the structural claims.
Kinds and varieties
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Racemic methadone free base
- Racemic methadone hydrochloride (the usual pharmacopoeial medicinal substance)
- Dilute oral mixture for supervised consumption (commonly 1 mg/mL)
- Oral concentrate (commonly 10 mg/mL)
- Immediate-release tablets or dispersible tablets
- Parenteral (injectable) solution
- Which of these kinds and varieties hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Identifiers and schemes
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Wikidata - Q179996 - Item for methadone as commonly understood; covers the racemate used in medicine.
- CAS Registry Number - 76-99-3 - Racemic methadone free base.
- CAS Registry Number - 1095-90-5 - Racemic methadone hydrochloride, the usual pharmaceutical salt.
- ATC - N07BC02 - Methadone as a drug used in opioid dependence.
- ATC - N02AC06 - Methadone as an analgesic (diphenylpropylamine derivative).
- UNII - UC6VBE7V1Z - FDA substance identifier for methadone (free base).
- UNII - 229809935B - FDA substance identifier for methadone hydrochloride.
- INN - methadone - International Nonproprietary Name; the INN denotes the racemate unless an enantiomer prefix is used.
- DEA ACSCN - 9250 - U.S. controlled-substance code for methadone (Schedule II).
- PubChem CID - 4095 - Compound record for methadone.
- InChIKey - USSIQXCVUWKGDB-UHFFFAOYSA-N - Standard InChIKey of the racemate (no stereodescriptor).
- DrugBank - DB00333 - DrugBank accession for methadone.
- Which of these identifiers and schemes hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Standards and regulation
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- USP monograph Methadone Hydrochloride (United States Pharmacopeial Convention)
- European Pharmacopoeia monograph Methadone hydrochloride (EDQM)
- WHO Model List of Essential Medicines: methadone for opioid dependence and pain (World Health Organization)
- Single Convention on Narcotic Drugs, 1961, as a narcotic under international control (United Nations / INCB)
- U.S. Controlled Substances Act Schedule II; DEA ACSCN 9250 (U.S. DEA)
- 42 CFR Part 8 certification of opioid treatment programs (SAMHSA, United States)
- U.S. FDA labeling with boxed warnings for respiratory depression, QT prolongation, and fatal accumulation during induction
- Misuse of Drugs Act 1971, Schedule 2 (United Kingdom)
- Which of these standards and regulation hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Real-world use
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Daily supervised oral dosing in opioid treatment programmes as agonist maintenance for heroin, fentanyl and other opioid dependence.
- Take-home oral doses after a patient is judged stable, typically as tablets or measured liquid.
- Around-the-clock analgesia for cancer and other severe chronic pain, especially when shorter-acting opioids have failed or caused incomplete relief.
- Continuation of maintenance (oral or parenteral) during hospital admission or perioperatively so that withdrawal does not interrupt care.
- Use in pregnancy for opioid use disorder, with the neonate then observed for opioid withdrawal.
- Forensic and clinical toxicology as a commonly detected prescription opioid in post-mortem and driving-under-the-influence casework.
- Which of these real-world use hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Typical measurements
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Typical oral maintenance dose in opioid agonist therapy - 60-120 (induction often starts much lower, e.g. 10-30) - mg/day
- Terminal elimination half-life - 8-59 (population mean near 24) - h
- Oral bioavailability - 70-80 (reported span roughly 36-100) - %
- Plasma protein binding - 85-90 - %
- Trough plasma concentration cited in TDM practice - 100-400 (poorly correlated with effect; highly individual) - µg/L
- Enantiomer composition of the racemate - 50:50 (R):(S) - mol %
- Which of these typical measurements hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Failure modes and hazards
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Fatal respiratory depression during induction or after a missed-dose restart, because accumulation over several days outruns incomplete cross-tolerance.
- Dose-related QT prolongation and torsades de pointes, driven largely by (S)-methadone block of hERG, worsened by high dose, hypokalaemia, and CYP2B6 or CYP3A4 inhibitors.
- Pharmacokinetic interactions (CYP2B6/3A4 inducers and inhibitors, including many antiretrovirals and anticonvulsants) that drop patients into withdrawal or push them into toxicity.
- Additive sedation and respiratory depression with benzodiazepines, alcohol and other CNS depressants.
- Diversion and injection of oral liquids or crushed tablets, with overdose and injection-site harm.
- Neonatal opioid withdrawal after in-utero exposure.
- Hepatic impairment slowing clearance and allowing delayed accumulation.
- Stigma and tightly clinic-bound dispensing that interrupt treatment and precipitate return to unregulated opioids.
- Which of these failure modes and hazards hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Regional variation
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- United States, Canada, the United Kingdom and Australia license and dispense the racemate; enantiopure levomethadone is not the routine product.
- Germany, Austria and some neighbouring systems commonly use levomethadone (L-Polamidon) at roughly half the milligram dose of the racemate.
- United Kingdom supervised consumption is classically a green 1 mg/mL oral mixture (DTF), whereas U.S. OTPs often use a 10 mg/mL concentrate diluted at the window.
- France dispenses methadone mainly through specialised centres as syrup or capsules, with a different take-home culture from U.S. OTPs.
- Several health systems have shifted first-line opioid agonist therapy toward buprenorphine, so methadone is encountered more as the second-line or high-tolerance option.
- Which of these regional variation hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Neighbouring kinds and how to tell them apart
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Levomethadone ((R)-methadone) - Enantiopure (R)-isomer; chiral HPLC, specific rotation, or an enantiomer-labelled product distinguishes it. Clinically about twice as potent per milligram at the µ-opioid receptor as the racemate.
- Esmethadone / dextromethadone ((S)-methadone) - The (S)-enantiomer has negligible µ-opioid maintenance activity and is developed as an NMDA-related agent; chiral analysis or the labelled drug substance separates it from (RS)-methadone.
- Buprenorphine - Partial µ-agonist with a respiratory ceiling; can precipitate withdrawal in a methadone-maintained patient. Immunoassay plus confirmatory chromatography, and the clinical precipitated-withdrawal test, separate the two.
- Morphine - Phenanthrene scaffold with a short duration and active glucuronide metabolites; GC-MS/LC-MS identification and the absence of the diphenylheptan-3-one core separate it.
- Levacetylmethadol (LAAM) - α-acetyl methadol analogue formerly used for thrice-weekly maintenance and withdrawn for arrhythmia; chemical identity (acetylated side chain) and historical product name separate it.
- Dipipanone - Related diphenylpropylamine opioid (often historically combined with cyclizine); chromatographic identity and the piperidino versus dimethylamino substitution distinguish it.
- Which of these neighbouring kinds and how to tell them apart hold for the sense of (RS)-methadone this model covers, and on what evidence? provenance
Sources
- USP monograph: Methadone Hydrochloride - Identity of the hydrochloride salt as the pharmacopoeial substance, and the distinction from the free base.
- European Pharmacopoeia monograph: Methadone hydrochloride - Ph. Eur. identity, assay and impurity control of the racemic hydrochloride.
- WHO Model List of Essential Medicines - Listing of methadone for opioid dependence and for pain, and its status as an essential medicine.
- Single Convention on Narcotic Drugs, 1961 - International scheduling of methadone as a narcotic drug under INCB control.
- Methadone hydrochloride prescribing information (U.S. FDA) - Approved uses, boxed warnings (respiratory depression, QT prolongation, accumulation on induction), and formulation types.
- Federal guidelines and 42 CFR Part 8 for opioid treatment programs (SAMHSA) - U.S. practice of daily supervised oral methadone in certified OTPs.
- IUPHAR/BPS Guide to PHARMACOLOGY: methadone - Receptor pharmacology: (R)-enantiomer carries essentially all µ-opioid agonist activity; (S)-enantiomer contributes NMDA antagonism and hERG block.
- PubChem Compound Summary: Methadone - CAS 76-99-3, InChIKey, and the racemate as the common chemical record.
What the second pass must settle
- Does the authoritative registry scope include methadone salts under vr.tr.rs-methadone, or require links to separate salt entries?
- Does an existing Vercy world model already own this concept, requiring this entry to link to it rather than create another publication?
- Which authoritative specifications and validated chiral methods establish the acceptable R/S interval for each intended material use?
- Which form-specific impurity limits, storage conditions and retest criteria should govern assessments of this entry?
- Which jurisdictions and institutional contexts must the model support, and how will their action-authorisation evidence be kept current?