Neratinib-d 6 (HKI-272-d6) is the deuterium labeled Neratinib. Neratinib (HKI-272) is an orally available, irreversible tyrosine kinase inhibitor with IC50s of 59 nM and 92 nM for HER2 and EGFR , respectively.
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.
Specifiche
Meccanismi biochimici e fisiologici
Neratinib-d 6 (HKI-272-d6) is the deuterium labeled Neratinib. Neratinib (HKI-272) is an orally available, irreversible tyrosine kinase inhibitor with IC50s of 59 nM and 92 nM for HER2 and EGFR , respectively.
Condizioni di conservazione di stoccaggio
Store at -20°C
Spedito in
Ice chest + Ice pads
Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.
This compound belongs to the class of organic compounds known as 4-aminoquinolines. These are organic compounds containing an amino group attached to the 4-position of a quinoline ring system.
External Descriptors
Not available
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.
Certificati (CoA, COO, BSE/TSE e tabella di analisi)
C of A & Other Certificates(BSE/TSE, COO):
Analytical Chart:
Calcolatori di soluzioni
Molarity Calculator
Determine the necessary mass, volume, or concentration for preparing a solution.
Dilution Calculator
Determine the dilution needed to prepare a stock solution.
Reconstitution Calculator
Recensioni
Recensioni dei clienti
Application Protocols
Validated, item-specific application protocols are not provided in the Product Data for SKU N647202. The following is general guidance for LC–MS/MS internal standard use; adapt to your SOPs:
General LC–MS/MS internal standard workflow (guidance):
Stock preparation: Dissolve Neratinib-d6 in anhydrous DMSO or acetonitrile to a known concentration (e.g., 1–5 mM). Store aliquots at −20°C.
Working internal standard solution: Dilute stock into acetonitrile/water (or methanol/water) to yield a concentration suitable for spiking (e.g., 10–500 ng/mL), ensuring solvent composition is compatible with the sample matrix.
Sample spiking: Add a fixed volume of internal standard solution to each calibration, QC, and unknown sample prior to extraction.
Extraction: Perform protein precipitation (3–5× organic), SPE, or LLE as validated. Evaporate and reconstitute in initial mobile phase when necessary.
Chromatography and detection: Use positive ESI with MRM transitions specific to the +6 Da analog. Co-elution with neratinib should be verified.
Item-specific parameters (recommended transitions, collision energies, retention time) are method-dependent and must be established experimentally. For any application outside analytical quantitation, consult the CoA/Spec Sheet and develop a fit-for-purpose protocol.
Biological Roles
Contextual, non-clinical information (literature/general knowledge):
Mechanistic class (parent scaffold): Neratinib is a small-molecule, covalent protein kinase inhibitor scaffold targeting the ErbB/HER family in biochemical systems. The d6 analog preserves binding and reactivity profiles but is deployed primarily as an analytical standard rather than as a functional probe.
Pathway relevance: In cell-free biochemical assays, the parent scaffold engages ATP-binding sites of kinases and can form covalent adducts with nucleophilic residues (e.g., cysteine) in susceptible kinases. Deuteration does not materially alter the biochemical interaction in typical assay timescales.
ADME/biotransformation research: Neratinib-d6 is valuable for tracking parent compound in complex matrices, distinguishing it from endogenous components, and supporting studies on absorption, distribution, metabolism (e.g., oxidative demethylation, hydrolysis), and extraction recovery.
Bioanalytical role: Used to normalize matrix effects and instrument variability in LC–MS/MS workflows for biological samples (plasma, serum, tissue homogenates, cell lysates). It aids in establishing accurate concentration–time profiles in non-clinical pharmacokinetic experiments.
Important limitations:
This product is supplied strictly for research use only (as stated in Product Data). No medical, diagnostic, or therapeutic use is intended or implied.
For any biological exposure studies, ensure appropriate institutional approvals and follow applicable biosafety and chemical safety procedures.
Buffer Applications
This item is not a buffer component and is not typically used to establish or maintain pH. Accordingly, conventional buffer-system recipes (e.g., phosphate, HEPES, Tris) do not apply.
Practical notes for assay buffers:
When preparing biological assay or extraction buffers that will contact Neratinib-d6, maintain low organic content during extraction only as needed for solubility, then adjust to LC–MS-compatible compositions (e.g., water with 0.1% formic acid and acetonitrile/methanol as organic modifier).
Avoid strong basic buffers for extended periods to minimize potential degradation of electrophilic motifs present in the parent scaffold.
For pH control and ionic strength, select standard biochemical buffers appropriate to your assay; Neratinib-d6 serves as an internal standard, not a buffering agent.
Green Alternatives
While Neratinib-d6 itself is a specialty analytical standard (no direct “green” substitute), greener choices can be made around its use, especially in sample preparation and chromatography.
Greener solvent choices (general guidance):
Replace DMF/DMAC with DMSO or propylene carbonate when solubility allows.
Favor acetonitrile over chloroform/dichloromethane for extractions compatible with LC–MS.
Consider ethanol or isopropanol for protein precipitation in place of acetonitrile when compatible with sensitivity and recovery.
MeOH/EtOH: Renewable routes exist; flammable but lower chronic toxicity.
2-MeTHF/CPME: Greener ethers for organic workups; typically not first-line for LC–MS standards but useful in synthetic sample cleanup upstream.
Operational improvements:
Miniaturize sample volumes and adopt microflow LC to reduce solvent use.
Use solid-phase extraction (SPE) with water-wettable sorbents to decrease organic solvent consumption and waste.
Implement energy-efficient cold storage and consolidate shipments to reduce cold-chain footprint.
Note: Any substitution must preserve analyte stability, recovery, and ionization efficiency. Validate changes with recovery and matrix-effect experiments before deployment in regulated assays.
Role: Neratinib-d6 is a stable-isotope-labeled analog used as an internal standard in analytical method development for pharmaceutical research. It supports quantitative analysis of neratinib in formulation development, stability studies, and process samples.
Pharmacopeial status: No pharmacopeial monograph for the deuterated analog is anticipated; use is governed by internal analytical SOPs and validation guidelines.
Matrix coverage: Useful across various matrices encountered in pharmaceutical R&D (e.g., dissolution media, excipient blends, process intermediates), provided chromatographic conditions achieve selective detection of the +6 Da analog.
Stability-indicating methods: Enables verification that specific degradants or process impurities are resolved from the analyte signal, with the d6 internal standard tracking sample preparation and instrument variability.
Restrictions:
Supplied strictly for research use only. Not for use in humans or for clinical diagnostic applications.
Documentation:
Maintain traceable records for lot numbers, preparation of reference solutions, and purity corrections when calculating reportable concentrations. Verify isotopic enrichment and purity against the CoA/Spec Sheet for SKU N647202.
Physical Properties
Item-specific physical data (from Product Data):
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.
Literature/general properties (for context; non-binding to this specific lot):
Physical state (typical for neratinib analogs): Solid, hydrophobic small molecule; often handled as a DMSO or acetonitrile stock for analytical work.
Solubility (typical practice): Moderately to highly soluble in polar aprotic organic solvents such as DMSO, DMF, and acetonitrile; very low aqueous solubility at neutral pH; solubility can improve in the presence of acid or co-solvents.
pKa/logP (parent neratinib, literature): Neratinib exhibits basic tertiary amine functionality (pKa for analogous scaffolds often in the 6–9 range) and high lipophilicity (logP typically >3). Exact values for the d6 analog depend on the specific isotopomer and should be determined experimentally.
Analytical notes:
Isotope effect: Deuteration minimally alters bulk physical properties but provides a +6 Da mass shift relative to the non-labeled parent, enabling selective quantification by MS.
For chromatographic use, expect nearly co-elution with the non-deuterated compound; minor retention shifts may occur depending on labeling site.
Always verify item-specific specifications (melting point, purity, water, residual solvents) on the CoA/Spec Sheet for this SKU.
Quality and Grades
Item-specific quality information (from Product Data):
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Professional guidance on deuterated reference standards:
Isotopic enrichment: For quantitative LC–MS/MS use, high deuterium incorporation and known labeling positions are critical to avoid interference from partially labeled isotopologues. The CoA should disclose the isotopic pattern (e.g., % d6, d5, etc.).
Analytical grade considerations: Reference standard/analytical grade materials typically feature low residual solvents, well-characterized identity (NMR, MS, HPLC/UPLC), and documentation suited to regulated workflows. In absence of a declared grade, verify chromatographic purity and isotopic enrichment on the CoA.
Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. If stabilizers are present for hygroscopicity or light sensitivity, they should be disclosed, as they can influence LC–MS ionization.
Traceability: Ensure lot-specific certificates include test methods, acceptance criteria, and reference spectra. For quantitation, a gravimetrically prepared, purity-corrected stock solution can improve accuracy.
Summary: Rely on the CoA/Spec Sheet for exact grade, purity, isotopic enrichment, and analytical testing applied to SKU N647202. For regulated bioanalytical workflows, document chain of custody and qualification to internal standards SOPs.
Reaction and Applications
This product is primarily a stable-isotope-labeled analytical standard rather than a synthetic building block. Its most relevant applications are in quantitative and mechanistic studies:
Analytical/quantitative applications:
LC–MS/MS internal standard: Neratinib-d6 co-elutes closely with neratinib and exhibits a +6 Da mass shift, enabling isotope-dilution quantification in biological matrices (plasma, tissue homogenate) or formulation studies. Improves accuracy by correcting for matrix effects and extraction recovery.
Calibration and QC: Employed to prepare multi-point calibration curves and quality-control samples in bioanalytical methods (e.g., MRM). Supports method validation parameters (linearity, accuracy, precision, carryover, stability) under regulatory guidance (e.g., typical bioanalytical method validation best practices).
Mechanistic/ADME research:
Metabolic tracing: Deuterium labels facilitate distinguishing parent drug from metabolites or back-exchange artifacts; helpful in metabolite ID and mass-balance studies.
Stability studies: Used to evaluate photolysis, hydrolysis, and oxidative stability relative to the unlabeled parent.
Practical notes:
Optimize MRM transitions to target the +6 Da precursor and signature fragments; ensure no overlap with endogenous signals.
Confirm the absence of significant H/D exchange under sample prep conditions. Favor aprotic solvents and neutral to slightly basic pH when feasible.
For extraction (protein precipitation, SPE), match the internal standard solvent and timing to the sample matrix to minimize bias.
Synthesis/bench chemistry: Not typically employed as a coupling partner or reagent; if used in reactivity studies, treat it as a tracer, not a stoichiometric reagent.
Reaction Conditions
As a specialty analytical standard, Neratinib-d6 is not typically used as a reagent in chemical reactions. Nevertheless, the following general conditions are relevant to its analytical deployment and stability studies (literature/general guidance):
Stock solutions: Prepare at 0.1–10 mM in anhydrous DMSO or acetonitrile. Store aliquots at ≤−20°C to minimize freeze–thaw cycles. Concentration and solvent choice should be finalized based on solubility and intended assay.
LC–MS/MS analysis:
Mobile phases: Water with 0.1% formic acid (A) and acetonitrile or methanol with 0.1% formic acid (B).
Columns: C18 or phenyl-hexyl, sub-2 µm for UPLC; temperature 30–50°C.
Detection: Positive ESI, multiple-reaction monitoring (MRM); precursor m/z shifted by +6 relative to neratinib. Optimize collision energies empirically.
Sample preparation: Protein precipitation with MeCN or MeOH (3–5× volume), SPE on reversed-phase sorbents, or liquid–liquid extraction using MTBE/EtOAc where compatible with recovery.
Stability checks: Conduct short-term autosampler stability (4–24 h at 4–10°C), bench-top stability (1–4 h), and freeze–thaw cycles (≥3) as part of method validation.
These are general, literature-style recommendations, not item-specific specifications. Validate and document final conditions according to your internal SOPs and regulatory guidance for bioanalytical methods.
Safety and Handling
Safety classification for this item (from Product Data):
Signal Word: Not specified for this item; refer to SDS.
H-Statements: Not specified for this item; refer to SDS.
GHS Classification: Not specified for this item; refer to SDS.
Pictograms: Not specified for this item; refer to SDS.
General laboratory safety (professional guidance):
PPE: Use lab coat, safety glasses, and appropriate gloves (e.g., nitrile). Handle powders/solids in a fume hood to avoid inhalation of dust/aerosols. Avoid skin and eye contact.
Handling: Prepare concentrated stocks in anhydrous DMSO or acetonitrile. Use amber vials or minimize light exposure if photosensitivity is suspected for the scaffold. Avoid prolonged contact with strong oxidizers.
Incompatibilities (general): Strong acids/bases may cause degradation; strong oxidants may react with heteroaromatic systems. Avoid moisture ingress for long-term stability of the solid.
Spill/Exposure: For small spills, absorb with inert material and dispose per institutional guidelines. In case of skin contact, wash with soap and water; for eye exposure, rinse with water for ≥15 minutes and seek medical attention as needed. If inhaled, move to fresh air; if ingested, seek medical attention.
Waste: Dispose as organic hazardous waste according to local regulations.
Authoritative safety and first-aid information must be obtained from the item-specific SDS. Conduct a risk assessment commensurate with your application and scale.
Solvent Selection
Use-case driven solvent guidance for Neratinib-d6 in analytical and research workflows:
Primary stock solvents (typical):
DMSO (anhydrous): Excellent solvating power for hydrophobic kinase inhibitor scaffolds; miscible with water for serial dilutions. Compatible with LC–MS.
Acetonitrile (MeCN): Volatile, MS-friendly, facilitates preparation of calibration standards and spiking solutions.
DMF: High solvency; use when DMSO/MeCN are insufficient. Less volatile; consider toxicity and cleanup.
Aqueous compatibility: Poor intrinsic aqueous solubility is expected; prepare aqueous working solutions by cosolvent dilution (e.g., 0.1–1% DMSO or MeCN in buffered water) or by acidified aqueous/organic mixtures for LC–MS sample preparation.
Polarity/miscibility (general): Non-ionic, lipophilic small molecule; favors polar aprotic organics. Avoid neat protic solvents for concentrated stocks due to limited solubility and potential degradation.
Small comparison (literature-based, general):
DMSO: highest solvency, low volatility; may suppress MS signal at high %.
MeCN: MS-ideal, volatile; slightly lower solvency vs DMSO but better for calibration curves.
Methanol: useful for sample prep; can promote side reactions in rare cases; watch for solubility.
Practical tips:
Filter working solutions (0.2 µm PTFE) to remove particulates prior to LC–MS.
Use amber vials and maintain cold conditions during long autosampler runs to minimize degradation.
Verify compatibility of plasticware; prefer glass for concentrated stocks.
Storage and Reconstitution
Item-specific instructions (from Product Data):
Storage Conditions: Store at −20°C.
Shipped In:Ice chest + Ice pads.
Additional professional guidance:
Container: Keep in tightly sealed, chemically compatible vials (preferably amber glass) with minimal headspace. If supplied as a film or powder, consider storing under inert gas (e.g., nitrogen) to limit oxidation and moisture uptake.
Aliquoting: Prepare single-use aliquots of stock solutions to avoid repeated freeze–thaw cycles. Record concentration and preparation date on each vial.
Reconstitution (general):
Solvents: Anhydrous DMSO or acetonitrile are preferred for initial dissolution.
Procedure: Allow vial to equilibrate to room temperature in a desiccator, quickly add measured solvent volume, vortex until fully dissolved, and, if needed, sonicate briefly. Filter through 0.2 µm PTFE for particulate removal.
Working solutions: Dilute into mobile phase-compatible mixtures (e.g., water/MeCN with 0.1% formic acid) immediately prior to use.
Stability: Item-specific stability (solid-state and in-solution) is not specified for this item; refer to CoA/Spec Sheet. As a general practice, minimize light exposure and maintain cold conditions during storage and autosampler runs.
Documentation: Record lot number, storage conditions, and usage history for traceability. Verify concentration periodically by UV or quantitative NMR if required by SOPs.
Always consult the item’s CoA and SDS for definitive handling and storage guidance for SKU N647202.
Structure and Identity
Brief description: Neratinib-d6 is a stable-isotope-labeled analog of neratinib, typically used as an internal standard for LC–MS/MS quantification and tracer studies in research workflows.
Item-specific identifiers (from Product Data):
SKU: N647202
Product Name: Neratinib-d6
CAS: 1259519-18-0
PubChem CID: 49870271
InChIKey: 171994 (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.
General structural notes (literature/general knowledge):
Compound type: Small-molecule, covalent kinase inhibitor analog; the d6 label denotes six deuterium atoms incorporated at defined positions (site-specific labeling varies by supplier and lot; consult CoA for exact isotopologue mapping).
Functional features (neratinib scaffold, literature): A heteroaromatic core bearing an electrophilic Michael acceptor (for covalent target engagement in the non-deuterated parent), along with aromatic/heteroaromatic rings and a tertiary amine side chain. Neratinib-d6 retains the same connectivity as neratinib, differing only by replacement of selected hydrogens with deuterium.
Stereochemistry: Neratinib and its deuterated analogs are typically achiral as free bases (literature). No stereocenters are expected.
2D description (literature): Multi-ring aromatic system with an acrylamide-like warhead conjugated to an anilide/heteroaryl unit and a dialkylamino-alkoxy side chain; deuteration appears on aliphatic and/or aromatic C–D positions without changing valence structure.
Note: For exact labeling positions, isotopic enrichment, and definitive identifiers (complete InChI/InChIKey, canonical SMILES), please consult the item’s CoA/Spec Sheet.
Synthetic Utility
Neratinib-d6 is not typically employed as a synthetic building block. However, in specialized research it can serve the following roles:
Tracer in reaction development: Monitor reaction progress or competitive binding/consumption relative to unlabeled neratinib via LC–MS by exploiting the +6 Da mass offset.
Mechanistic probes: Evaluate isotopic effects on specific transformation steps (e.g., oxidative metabolism mimics or base-catalyzed degradation) to assess kinetic isotope effects, though such effects are usually subtle for non-exchangeable C–D positions.
Degradation pathway mapping: Subject both labeled and unlabeled materials to stress conditions (acid/base/oxidative/thermal) to correlate fragment ions and confirm structural assignments in LC–MS/MS.
Considerations:
Because deuteration can cause minor chromatographic retention shifts, co-injection with the unlabeled analog under identical conditions is recommended for accurate comparative studies.
Avoid conditions that promote H/D exchange if deuterium is located at exchangeable positions (verify labeling site on the CoA). Aprotic solvents and neutral pH reduce exchange risk.
For traditional synthetic transformations (cross-coupling, amide formation, etc.), use the unlabeled parent compound to conserve the labeled material for analytical purposes, reserving Neratinib-d6 for control/tracing experiments.
Target Specificity
Only item-specific target data should be presented here. Product Data for SKU N647202 does not include target binding or specificity information.
Target/Antigen: Not specified for this item; refer to CoA/Spec Sheet.
Epitope/Binding site: Not specified for this item; refer to CoA/Spec Sheet.
Species reactivity/Selectivity: Not specified for this item; refer to CoA/Spec Sheet.
Note: While the non-deuterated parent compound is known in the literature as a kinase-targeted small molecule, this deuterated product is sold as a research chemical/analytical standard, and no target-specific performance claims are made for this SKU.
Domande frequenti
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 1259519-18-0, the molecular formula is C30H23D6ClN6O3, and the molecular weight is 563.08 g/mol. InChIKey JWNPDZNEKVCWMY-CJSPGLJTSA-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.
Utilizziamo i cookie per garantire il corretto funzionamento del sito web e, ove consentito, per migliorare la tua esperienza. Puoi gestire le tue preferenze in qualsiasi momento nelle Impostazioni. Per saperne di più, consulta la nostra Cookie Policy.
Desidera che le inviamo un messaggio quando avremo sconti disponibili?
Ricordamelo più tardi
Grazie! Controlli la sua casella di posta per confermare.
Products are supplied to verified businesses, institutions, and qualified professionals for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
