1. Product Overview
Imatinib N-Desmethyl Impurity (CAS 331771-20-1) is a key pharmaceutical impurity and reference standard derived from the N-demethylation of Imatinib (Gleevec/Glivec), a first-in-class BCR-ABL tyrosine kinase inhibitor. This compound, also known as N-Desmethyl Imatinib or STI-571 Impurity J, results from the oxidative removal of one methyl group from the piperazinyl nitrogen. With the molecular formula C₂₈H₃₀N₆O and a molecular weight of 466.58 g/mol, it is an essential analytical reference standard for quality control, method development, and regulatory filing in the manufacturing of Imatinib API and formulations.
2. Key Features and Benefits
• Regulatory-Grade Standard: Essential for ANDA (Abbreviated New Drug Application) and NDA (New Drug Application) submissions, providing a certified reference for impurity profiling and method validation.
• High Purity & Batch Traceability: Supplied at ≥95% or ≥98% (HPLC), with full Certificate of Analysis (CoA) including ¹H NMR, LC-MS, and HPLC verification for each lot.
• Structural Fidelity: The N-desmethyl metabolite is a known human impurity of Imatinib; this standard enables accurate quantification of impurity levels in API batches to meet ICH (International Council for Harmonisation) guidelines.
• Stable Solid Form: White to off-white crystalline solid with good shelf stability under recommended storage conditions, minimizing the need for frequent re-certification.
• Multi-Use Reference: Suitable for use in HPLC, UPLC, LC-MS, and other analytical techniques for method development, system suitability testing, and stability studies.
3. Major Applications
• Pharmaceutical Quality Control (QC): Used as a reference standard for the identification and quantification of N-desmethyl Imatinib impurity in Imatinib API and finished drug products (tablets, capsules).
• Analytical Method Development: Employed in the development and validation of HPLC/UV, LC-MS/MS, and other analytical methods for Imatinib impurity profiling in compliance with USP, EP, and JP standards.
• Regulatory Filing Support: Provides essential data for ANDA/NDA submissions, including impurity characterization, forced degradation studies, and stability testing.
• Metabolite & Pharmacokinetic Studies: Serves as a reference for the major human metabolite of Imatinib (CYP3A4/1A2-mediated N-demethylation), aiding in metabolism and pharmacokinetic research.
• Research & Development: Used in academic and industrial R&D for studying structure-activity relationships (SAR) of Imatinib analogs and the impact of N-alkylation on kinase binding affinity.
4. Technical Specifications
Item Description
Product Name Imatinib N-Desmethyl Impurity (STI-571 Impurity J)
Synonyms N-Desmethyl Imatinib; 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-(3-pyridinyl)-2-pyrimidinyl]benzamide; STI-571 Impurity J; Gleevec N-Desmethyl Impurity
CAS Number 331771-20-1
Molecular Formula C₂₈H₃₀N₆O
Molecular Weight 466.58 g/mol
MDL Number MFCD28397837
Assay (Purity) ≥95% / ≥98% (HPLC)
Appearance White to off-white crystalline solid or powder
Melting Point Not reported (typical for Imatinib analogs: 200–250 °C, decomposes)
Boiling Point ~706.5 °C (Predicted)
Density ~1.25 g/cm³ (Predicted)
pKa (Predicted) ~7.5–8.5 (Piperazine N); ~3.5 (Benzamide NH)
Calculated LogP ~3.5–4.0
Polar Surface Area (PSA) ~73.0 Ų
Hydrogen Bond Donors 1
Hydrogen Bond Acceptors 6
Rotatable Bonds 7
Solubility Soluble: DMSO (>50 mg/mL, sonication recommended), DMF, Methanol (slightly), Ethanol (slightly), Acetic acid.
Slightly Soluble:Water (very low aqueous solubility; can be dissolved as hydrochloride or methanesulfonate salt).
Insoluble:Hexane, Ether.
Spectral Data (Predicted) ¹H NMR (DMSO‑d₆, 400 MHz): δ 2.20 (s, 3H, N-CH₃), 2.45–3.65 (m, 10H, piperazine-CH₂), 4.50 (s, 2H, N-CH₂-Ar), 7.10–8.80 (m, 10H, aromatic + pyrimidine + pyridine H), 10.5 (br s, 1H, CONH).
¹³C NMR (DMSO‑d₆):δ 28.0 (N-CH₃), 45–55 (piperazine Cs), 55.0 (N-CH₂-Ar), 110–160 (aromatic + heteroaromatic Cs), 165.0 (C=O), 168.0 (C=O, benzamide).
SMILES CN1CCN(CC1)CC2=CC=C(C=C2)C(=O)NC3=NC=CC(=N3)C4=CC=CC=N4
InChI Key HSDVBTXOBHGGNV-UHFFFAOYSA-N
Storage (Powder) 2–8 °C or -20 °C, sealed, protected from light & moisture; stable ≥18–24 months
HS Code 2933.99.90 / 3822.90.00 (Reference Standard)
5. Storage and Handling
• Storage: Store in a tightly sealed container at 2–8 °C (or -20 °C for long-term), protected from light and moisture. For long-term storage (>12 months), keep in a desiccator. Stable for at least 18–24 months from date of manufacture.
• Handling: Allow vial to reach room temperature before opening to prevent moisture condensation. Dissolve in anhydrous DMSO, DMF, MeOH, or DCM as required. For aqueous work, the free base can be converted to a water-soluble salt by adding 1 eq. of HCl in MeOH or methanesulfonic acid.
• Solution Preparation: Prepare stock solutions in anhydrous DMSO (10–50 mM). The compound may require gentle warming (≤50 °C) and sonication for complete dissolution. Protect from light.
• Solution Stability: DMSO or methanolic stocks are stable at -20 °C for 1–3 months. Avoid repeated freeze-thaw cycles; aliquot upon preparation.
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H302: Harmful if swallowed.
• H315: Causes skin irritation.
• H319: Causes serious eye irritation.
• H335: May cause respiratory irritation.
• H351: Suspected of causing cancer (structural alert based on aromatic amine/amide—handle with caution).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P261: Avoid breathing dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P271: Use only outdoors or in a well-ventilated area.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.
• P301+P312: IF SWALLOWED: Call a POISON CENTER or physician if you feel unwell.
• P302+P352: IF ON SKIN: Wash with plenty of soap and water.
• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.
• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
• P308+P313: IF exposed: Get medical advice/attention.
• P330: Rinse mouth if swallowed.
• P337+P313: If eye irritation persists: Get medical advice/attention.
• P403+P233: Store in a well-ventilated place. Keep container tightly closed.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Seek medical advice.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce irritating/acrid smoke (CO, NOₓ). Nitrogen oxides are toxic.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do not allow entry to drains or waterways. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood. Keep container closed when not in use. Store at 2–8 °C (or -20 °C), protected from light and moisture. Keep away from strong oxidizers and strong acids/bases.
• Hazardous Decomposition Products: Nitrogen oxides (NOₓ), carbon monoxide (CO), carbon dioxide (CO₂).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potentially bioactive and genotoxic compound (structural alert present).
