Teriflunomide-d4 , CAS No.1185240-22-5

CAS: 1185240-22-5 Cat. No.: T651973 Formula: C₁₂H₅D₄F₃N₂O₂ Molecular Weight: 274.23 EC Number: 111-134-5 PubChem CID: 71313485

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Teriflunomide-d 4 is deuterium labeled Teriflunomide.

In Vitro

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Specifications

Biochemical and Physiological Mechanisms

Teriflunomide-d 4 is deuterium labeled Teriflunomide.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Names and Identifiers

Canonical Smiles

CC(=C(C#N)C(=O)NC1=CC=C(C=C1)C(F)(F)F)O

IUPAC Name

(Z)-2-cyano-3-hydroxy-N-[2,3,5,6-tetradeuterio-4-(trifluoromethyl)phenyl]but-2-enamide

InChIKey

UTNUDOFZCWSZMS-KXFGXCNQSA-N

INCHI

1S/C12H9F3N2O2/c1-7(18)10(6-16)11(19)17-9-4-2-8(3-5-9)12(13,14)15/h2-5,18H,1H3,(H,17,19)/b10-7-/i2D,3D,4D,5D

Isomeric SMILES

[2H]C1=C(C(=C(C(=C1C(F)(F)F)[2H])[2H])NC(=O)/C(=C(/C)\O)/C#N)[2H]

PubChem CID

71313485

Molecular Weight

274.23

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Trifluoromethylbenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Trifluoromethylbenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Trifluoromethylbenzenes
• Alternative Parents: Anilides N-arylamides Vinylogous acids Secondary carboxylic acid amides Nitriles Enols Organofluorides Organic oxides Hydrocarbon derivatives Carbonyl compounds Alkyl fluorides
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Trifluoromethylbenzene - Anilide - N-arylamide - Vinylogous acid - Carboxamide group - Secondary carboxylic acid amide - Carboxylic acid derivative - Enol - Carbonitrile - Nitrile - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Carbonyl group - Alkyl halide - Alkyl fluoride - Organic nitrogen compound - Organic oxygen compound - Cyanide - Organic oxide - Hydrocarbon derivative - Aromatic homomonocyclic compound
• Description: This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Application Protocols

Example LC–MS/MS workflow for quantitative analysis using teriflunomide‑d4 (general guidance; adapt to your SOP):

• Materials
  • Teriflunomide‑d4 stock solution (prepared in acetonitrile or DMSO), analyte standard (teriflunomide), LC–MS grade solvents, calibration matrix (e.g., stripped plasma) if applicable.
• Calibration and QC preparation
  • Prepare a serial dilution of teriflunomide standards across the expected range. Spike a fixed concentration of teriflunomide‑d4 into all calibrators, QCs, and unknowns at a concentration that yields comparable signal to mid‑range analyte.
• Sample processing (protein precipitation example)
  • Aliquot matrix; add internal standard; precipitate proteins with 3–4 volumes of cold acetonitrile or methanol; vortex and centrifuge. Transfer supernatant to LC vials.
• Chromatography (representative guidance)
  • Reversed‑phase C18 column; water/acetonitrile with 0.1% formic acid or ammonium formate buffer; gradient elution to 60–90% organic; column temperature controlled to improve retention reproducibility.
• MS/MS detection
  • Negative or positive ESI depending on method optimization; monitor multiple reaction monitoring (MRM) transitions for teriflunomide and the +4 Da isotopolog. Verify absence of isotopic overlap/interference.
• Data analysis
  • Construct calibration curves using analyte-to-IS peak area ratios; apply appropriate weighting (e.g., 1/x or 1/x^2). Evaluate accuracy, precision, carryover, recovery, and matrix effects per validation guidelines.

Note: The above is general literature-style guidance; specific instrument parameters and validated transitions should be developed in-house.

Biological Roles

This section provides general literature context about the unlabeled parent compound; it does not imply biological testing of this product.

• Parent compound (teriflunomide) role (literature)
  • Teriflunomide is known as a selective inhibitor of dihydroorotate dehydrogenase (DHODH), a key mitochondrial enzyme in de novo pyrimidine biosynthesis. Inhibition reduces the cellular pools of UMP/UDP/UTP, impacting rapidly proliferating cells.
  • The molecule’s structure (para‑CF3 phenyl, conjugated enol‑amide, nitrile) contributes to its binding and physicochemical profile.
• Isotopologue behavior
  • Teriflunomide‑d4 is chemically and biologically equivalent to the parent for most non-kinetic processes; deuterium substitution at non‑exchangeable positions minimally perturbs binding/partitioning. It is therefore well suited as an internal standard for quantifying teriflunomide in complex matrices.
• Research implications
  • Enables accurate measurement of teriflunomide concentrations in biochemical assays and cell/tissue extracts to correlate exposure with DHODH pathway engagement.

Note: No biological activity, potency, or therapeutic claims are made for this catalog item. Use is restricted to research and analytical applications.

Buffer Applications

Teriflunomide‑d4 is not a buffering reagent and is not used to control pH. Accordingly, classical buffer formulations (phosphate, Tris, HEPES, etc.) are not applicable.

Practical note

• When preparing aqueous working solutions for LC–MS, use volatile, MS‑compatible buffers (e.g., 0.1% formic acid or ammonium formate/acetate at low mM levels) only to the extent required by your chromatographic method. The compound itself does not provide buffering capacity.

Green Alternatives

As a solid analytical standard, the principal sustainability lever is solvent selection and sample‑handling practice rather than replacement of the analyte itself.

Greener choices for preparing and running standards (literature‑based guidance):

• Preferred solvents and trade‑offs
  • Acetonitrile (LC–MS grade): Common choice in bioanalysis; relatively favorable EHS profile versus chlorinated solvents and DMF. Highly volatile, enabling lower energy for solvent removal; flammable and requires appropriate ventilation.
  • Ethanol or aqueous ethanol: Potentially greener alternative for intermediate dilutions when method allows; may impact retention/ionization and solubility—validate before adoption.
  • 2‑Propanol: Can supplement water to aid solubility; higher viscosity may affect LC performance; assess ionization effects.
• Avoid where possible
  • DMF and dichloromethane for routine LC–MS standards due to toxicity and waste concerns; use only if method performance mandates.

Simple comparison (general, not item-specific):

• Acetonitrile: MS‑friendly, low viscosity, good solvency; derived from petrochemical feedstocks.
• Methanol: MS‑friendly, biodegradable; can be biobased; slightly different elution/ionization profile.
• Ethanol: Renewable sources available; may reduce method sensitivity for some analytes.

Operational practices

• Use micro‑aliquots to minimize waste, adopt low‑volume autosampler vials, and consolidate calibration ranges to reduce solvent consumption.
• Employ closed‑loop solvent capture on LC systems where feasible.

Pharmaceutical Uses

No excipient or pharmacopeial grade information is provided for this item. This product is supplied for research use only and is not intended for human or veterinary use.

Relevant research/manufacturing contexts (non-clinical, literature-informed):

• Reference standard
  • Teriflunomide‑d4 is commonly employed as an internal standard for quantitative analysis of teriflunomide in development and quality-control laboratories, including assessment of drug substance/drug product, stability studies, and in vitro ADME experiments.
• Process analytics
  • Supports method transfer and validation across laboratories by providing an isotopically distinguishable standard with coelution behavior similar to the analyte.
• Formulation R&D support
  • Facilitates forced‑degradation and compatibility studies by enabling accurate mass‑spectrometric tracking of teriflunomide in complex excipient matrices.

No claims are made regarding compliance with USP/EP monographs, GMP suitability, or clinical diagnostic use for this item.

Physical Properties

Item-specific physicochemical specifications have not been provided for this catalog entry.

• Item-specific values
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting point, boiling point, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• General/literature guidance for teriflunomide and its deuterated analogs (non-binding)
  • Physical state: typically an off‑white to pale solid for unlabeled teriflunomide; stable‑isotope analogs are similar in form (literature).
  • Solubility profile: sparingly soluble in water; readily soluble in polar aprotic organic solvents (DMSO, DMF, acetonitrile) and moderately soluble in alcohols (literature). Deuteration does not materially change bulk solubility.
  • Acid/base: neutral, weakly acidic enol amide; no significant ionization in neutral aqueous media (literature). pKa values are formulation‑dependent; consult primary sources for numerical values.
  • Partitioning: moderate hydrophobicity due to para‑CF3 phenyl and conjugated framework (literature). Exact logP/logD values for this labeled item are not specified here.
• Practical implications
  • For LC–MS work, prepare concentrated stocks in anhydrous acetonitrile or DMSO, then dilute into aqueous mobile phase containing organic modifier (e.g., 0.1% formic acid in water/MeCN) immediately prior to use to minimize precipitation.

For authoritative, item-specific data, always consult the CoA/Spec Sheet.

Quality & Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Research Use Note: For research use only.

Interpretation and best practices for this class of material:

• Stable‑isotope labeled reference standards
  • Typically supplied at high chemical purity with defined isotopic enrichment (e.g., ≥98 atom % D at labeled positions) and low levels of unlabeled isotopologues. For this item, exact enrichment and residual protium content are not specified; consult the CoA for quantitative values.
  • Trace level specifications relevant to LC–MS (residual solvents, inorganic salts, water content) are vendor/lot‑specific. In absence of listed specs, verify suitability by test injections and calibration.
• What the grade implies in practice
  • LC–MS/analytical grade materials are optimized for chromatographic cleanliness and well‑resolved isotopic patterns. If the grade is analytical or higher, you can expect low background in typical UV/MS detection. If the grade is not declared, perform a quick blank/standard run to ensure no carryover or interfering peaks in your method.
• Stabilizers
  • No stabilizer is indicated in the Product Data. If present, stabilizers would be declared on the CoA. The absence of a listed stabilizer suggests the neat solid is provided.

Recommendation: Review the lot-specific CoA for purity, isotopic enrichment, residual unlabeled teriflunomide, and any method-suitability notes before critical quantitative work.

Reaction & Applications

This material is primarily intended as a stable‑isotope–labeled reference standard rather than a synthetic reagent.

• Analytical applications (primary use)
  • Internal standard for quantitative LC–MS/MS of teriflunomide in biological and environmental matrices, enabling correction for matrix effects, extraction recovery, and instrument variability via stable isotope dilution.
  • Calibration and QC samples in method development/validation (linearity, accuracy, precision, stability) following regulatory guidance for small‑molecule bioanalysis (e.g., recovery and matrix‑matched calibration).
• Sample preparation contexts
  • Protein precipitation workflows using acetonitrile or methanol with isotopically labeled internal standard spiked pre‑extraction.
  • Solid‑phase extraction (SPE) or liquid–liquid extraction (LLE) for cleaner baseline when high sensitivity is required; deuterated analog tracks the parent through processing.
• Why deuterium labeling works
  • d4 analog coelutes closely with the unlabeled analyte in reversed‑phase LC while being baseline‑separable by mass (Δm ≈ +4 Da for the molecular ion), allowing robust isotope dilution quantitation without significant chromatographic isotope effects.
• Secondary research uses
  • Metabolic stability and transformation studies where the labeled internal standard assists in distinguishing parent from metabolites and in assessing isotope effects (usually negligible for deuterium at non-exchangeable sites under LC–MS conditions).

Note: This product is not generally used as a substrate or coupling partner in synthetic reactions; see Synthetic Utility and Application Protocols for analytical use details.

Reaction Conditions

Conventional reaction conditions are not applicable because teriflunomide‑d4 is used as an analytical standard rather than as a synthetic reagent. The following guidance instead focuses on preparing LC–MS calibration and QC samples (general, literature-based best practices):

• Stock solution preparation
  • Dissolve the solid in LC–MS grade acetonitrile or anhydrous DMSO to prepare a concentrated stock (e.g., 1–10 mg/mL). Vortex and, if needed, sonicate briefly. Record exact mass and final volume for gravimetric accuracy.
• Working solutions
  • Serially dilute stocks into acetonitrile or methanol, then into aqueous mobile phase or surrogate matrix as required. Aim to keep organic content consistent across calibrators and QCs to minimize matrix/solvent effects.
• Spike timing
  • For quantitative bioanalysis, add the internal standard prior to extraction (protein precipitation, LLE, or SPE) to compensate for recovery losses.
• LC–MS/MS considerations
  • Choose transitions separated by +4 Da relative to the analyte. Optimize source conditions to minimize H/D exchange (usually negligible for non-exchangeable labels). Validate lack of cross‑talk between channels.
• Stability checks
  • Assess bench‑top, autosampler, freeze–thaw, and long‑term storage stability for both analyte and internal standard under your specific conditions.

All numerical concentrations and conditions should be established and validated within your laboratory’s method parameters.

Safety & Handling

• GHS/SDS status
  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • GHS Classification/Pictograms: Not specified for this item; refer to SDS.
• General laboratory precautions (best practice for aryl amide/nitrile small molecules)
  • Handle in a fume hood; avoid inhalation of dust or aerosols. Use appropriate PPE: lab coat, safety glasses, and nitrile gloves.
  • Avoid contact with strong oxidizers and strong bases that may induce degradation or isomerization; store segregated from incompatible reagents.
  • Solutions in DMSO/DMF can enhance dermal absorption—prevent skin contact.
• First-aid overview (refer to SDS for full instructions)
  • Inhalation: Move to fresh air; seek medical attention if symptoms occur.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; obtain medical advice if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill and disposal
  • Small spills: Absorb with inert material, collect in a chemical waste container. Decontaminate area with suitable solvent while maintaining ventilation.
  • Dispose of solids and solutions through licensed chemical waste streams; do not discharge to drains.
• Stability considerations
  • Protect from light and moisture. Avoid repeated freeze–thaw of stock solutions to limit hydrolysis or isomerization of the conjugated amide/enol system.

Always defer to the product’s SDS for authoritative hazard classification and response guidance.

Solvent Selection

For teriflunomide‑d4 used as an LC–MS internal standard or analytical reference, solvent choice should prioritize solubility, stability, and MS compatibility.

• Solubility and polarity (literature guidance, parent compound)
  • Sparingly soluble in water; readily soluble in polar aprotic solvents (DMSO, DMF, acetonitrile). Moderate solubility in methanol/ethanol.
• Recommended stock solvents
  • DMSO (anhydrous): excellent solubilizer for concentrated stocks (e.g., 10–50 mM); aliquot to minimize freeze–thaw.
  • Acetonitrile (LC–MS grade): ideal for working standards and direct compatibility with reversed‑phase LC–MS mobile phases.
  • Methanol (LC–MS grade): useful for calibration standards; may reduce precipitation upon aqueous dilution versus acetonitrile in some methods.
• Aqueous handling
  • Prepare working solutions by diluting organic stocks into aqueous buffered mobile phase just before use. Add organic to aqueous while vortexing to avoid local supersaturation.
• Comparison considerations
  • DMSO: maximum solubility and stability; less volatile—good for long‑term stocks, but watch for ion suppression at high percentages in ESI.
  • Acetonitrile: highly volatile and MS‑friendly; lower viscosity improves LC performance; slightly lower solubility than DMSO.
  • Methanol: protic; can alter retention and ionization; sometimes improves peak shape for phenyl‑CF3 analytes.
• Avoid
  • Strongly basic aqueous media that may induce isomerization or hydrolysis over time; prolonged exposure to high pH is discouraged for standards.

Select your solvent system based on the demands of your LC–MS method (ionization mode, gradient, and sample matrix).

Storage & Reconstitution

• Storage (item-specific)
  • Store at -20°C (from Product Data). Protect from light and moisture. Keep tightly closed in the original container.
  • Shipped in: Ice chest + Ice pads (from Product Data) to maintain low temperature during transit.
• Shelf-life
  • Not specified for this item; refer to CoA/Spec Sheet. As a best practice, monitor by periodic LC–MS check injections.
• Reconstitution and handling (general best practice)
  • Allow vial to equilibrate to room temperature in a desiccator before opening to prevent condensation.
  • Prepare concentrated stocks in LC–MS grade acetonitrile or anhydrous DMSO. Record gravimetric additions for traceable concentration.
  • Filter solutions through 0.2 µm PTFE syringe filters if particulate is observed. Avoid aqueous media for long‑term stocks.
• Aliquoting
  • Divide stock solution into single‑use aliquots (amber vials) to minimize freeze–thaw cycles. Purge headspace with inert gas if long‑term storage is planned.
• Stability of solutions
  • Short‑term room temperature and autosampler stability are method‑dependent; verify empirically. Store working solutions at 2–8°C for short periods and at -20°C for longer terms where compatible with solvent.

Always consult the lot-specific CoA and SDS for definitive handling, storage limits, and any additional instructions.

Structure & Identity

Teriflunomide‑d4 is a stable‑isotope–labeled analog of teriflunomide, intended for quantitative analytical workflows and mechanistic research.

• Item-specific identifiers (from Product Data)
  • SKU: T651973
  • CAS: 1185240-22-5
  • CID: 71313485
  • InChIKey: 368836 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• Structural features (literature, parent compound)
  • Teriflunomide is the active metabolite of leflunomide and is a substituted anilide bearing a para‑trifluoromethyl phenyl ring, a conjugated enone/enol amide system, and a nitrile (–C≡N) functionality; it exists predominantly as the Z‑enol amide tautomer in solution (literature).
  • Teriflunomide‑d4 contains four deuterium atoms replacing four protium positions of teriflunomide; exact labeling sites vary by supplier. For this item, labeling pattern is not specified; refer to CoA/Spec Sheet.
• 2D description (literature, parent compound)
  • A para‑CF3 phenyl ring attached via an amide nitrogen to a conjugated C=C–C(=O)–N framework bearing a cyano substituent and an enolic hydroxyl. The deuterium atoms are isotopic substitutions that preserve valency and overall connectivity.

Note: All item-specific identifiers above are taken directly from Product Data; structural descriptions are general literature notes about the non-deuterated parent.

Synthetic Utility

As a deuterated analog of a specific small molecule, teriflunomide‑d4 is not typically employed as a building block in synthesis. Its value lies in its isotopic label for analytical chemistry.

Analytical/synthetic interface (general guidance):

• Isotopic tracing
  • Can be used in mechanistic or degradation studies to track isotope incorporation or exchange if deuteration occurs at non‑exchangeable positions. Deuterium placement dictates utility; verify labeling pattern from the CoA.
• Reference for impurity profiling
  • Supports assignment of mass spectral fragments and confirmation of product identity in synthetic routes targeting teriflunomide or analogs, via characteristic +4 Da mass shift of parent and fragments that retain labeled positions.
• Not recommended as a reagent
  • Due to cost and lack of functional handles intended for further transformation, this isotopolog is not chosen as a general precursor for synthesis. Use the unlabeled compound for reaction development and the d4 analog for analytics.

Target Specificity

This product is a small‑molecule standard, not an antibody or affinity reagent. Therefore, target specificity parameters such as antigen, epitope, clone, isotype, and species reactivity are not applicable.

Relevance note

• In analytical use, “specificity” arises from chromatographic separation and mass‑spectrometric detection of the teriflunomide/teriflunomide‑d4 pair rather than from biomolecular recognition.

Frequently Asked Questions

How should this product be stored?

Store at ?20 °C. Freezer storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1185240-22-5, the molecular formula is C12H5D4F3N2O2, and the molecular weight is 274.23 g/mol. InChIKey UTNUDOFZCWSZMS-KXFGXCNQSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.