Sorafenib Tosylate is an oral, small-molecule multikinase inhibitor targeting serine/threonine and receptor tyrosine kinases, including Raf kinases, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-beta. It suppresses tumor cell proliferation and tumor angiogenesis. Produced under strictly controlled current Good Manufacturing Practice guidelines, this active pharmaceutical ingredient is synthesized via optimized multi-step coupling routes designed to ensure high stereochemical purity and low residual transition metal levels. It is supplied as a crystalline solid optimized for downstream solid oral dosage manufacturing, meeting pharmacopeial standards suitable for global formulation projects.
Product Information
|
Parameter |
Technical Specification / Detail |
|
International Nonproprietary Name |
Sorafenib Tosylate |
|
CAS Registry Number |
284461-73-0 (Sorafenib Tosylate) / 475207-59-1 (Free base) |
|
Chemical Name |
4-{4-[3-(4-chloro-3-trifluoromethylphenyl)ureido]phenoxy}-N-methylpyridine-2-carboxamide 4-methylbenzenesulfonate |
|
Structural Classification |
Diaryl urea derivative, multikinase inhibitor API |
|
Appearance |
White to yellowish crystalline powder |
|
Solubility |
Practically insoluble in water; slightly soluble in ethanol; moderately soluble in DMSO |
|
Melting Range |
225°C to 235°C (with decomposition) |
|
Storage Conditions |
Store in tight containers protected from light and moisture at 20°C to 25°C |
|
Shelf Life |
36 months from manufacturing date under sealed conditions |
Quality & Specification
|
Analytical Test Parameter |
Acceptance Criteria (Specification) |
Test Method |
|
Assay (Anhydrous basis) |
98.0% – 102.0% |
High-Performance Liquid Chromatography |
|
Appearance of Solution |
Clear and practically colorless (0.5 g in 25 mL DMF) |
Visual Inspection / Ph. Eur. |
|
Water Content |
≤ 1.0% w/w |
Coulometric Karl Fischer Titration |
|
Residue on Ignition |
≤ 0.1% |
Gravimetric Analysis |
|
Heavy Metals |
≤ 20 ppm |
Atomic Absorption Spectroscopy / ICP-MS |
|
Individual Specified Impurity |
≤ 0.10% |
Gradient HPLC |
|
Total Impurities |
≤ 0.50% |
Gradient HPLC |
|
Residual Solvents |
Ethanol ≤ 5000 ppm, Ethyl Acetate ≤ 5000 ppm |
Headspace Gas Chromatography |
|
Particle Size Distribution (d90) |
10 µm – 50 µm (Customizable upon request) |
Laser Diffraction |
Manufacturing & Supply
|
Operational Parameter |
Specification & Facility Standard |
|
Synthesis Route |
Multi-step condensation and salt-formation using analytical-grade reagents with validated purge efficiency |
|
Cleanroom Classification |
ISO Class 8 cleanrooms for intermediate isolation; ISO Class 7 for final micronization and packaging |
|
Isolation & Drying |
Enclosed filter-dryer systems operating under nitrogen blanket to minimize polymorphic variation and moisture absorption |
|
Batch Scale |
Commercial scale capacity ranging from 100 kg to multi-metric tons per annum |
|
Supply Continuity |
Dual-sourcing raw material validation, established buffer inventory programs, and scheduled campaign production |
Documentation
Drug Master File: Open and closed part documentation available for regulatory filing support in major international jurisdictions.
Certificate of Analysis: Provided with every commercial and validation batch, detailing complete physical, chemical, and chromatographic results.
Good Manufacturing Practice: Issued by national competent authorities; audit reports available under confidentiality agreement.
Certificate of Suitability: Reference dossier aligned with European Pharmacopoeia monographs.
Safety Data Sheet: Compliant with Globally Harmonized System classification standards, containing occupational exposure limits.
Impurities Profile Statement: Comprehensive report covering synthetic by-products, degradation products, and genotoxic impurity risk assessments.
BSE/TSE Statement: Certified free from animal-origin raw materials, eliminating transmissible spongiform encephalopathy risks.
Packaging
Primary Packaging: Food-grade double-polyethylene bag, heat-sealed under laminar flow hood.
Secondary Packaging: Aluminum-foil barrier liner vacuum-sealed to prevent moisture ingress and oxidation.
Tertiary Packaging: Rigid fiber drum or UN-certified corrugated cardboard box with tamper-evident seals.
Labeling Standard: Batch number, manufacturing date, retest date, net weight, storage instructions, and hazard symbols in compliance with regulatory mandates.
Pharmaceutical Application
Hepatocellular Carcinoma Treatment: Formulated into immediate-release oral tablets indicated for the treatment of unresectable hepatocellular carcinoma by inhibiting tumor cell proliferation through targeted kinase suppression.
Advanced Renal Cell Carcinoma Therapy: Utilized in the production of solid oral dosage forms for advanced renal cell carcinoma management, where high purity profiles prevent interference with therapeutic plasma concentration curves.
Differentiated Thyroid Carcinoma Management: Integrated into targeted oncology drug products for locally recurrent, metastatic, progressive, or radioiodine-refractory differentiated thyroid carcinoma, supported by strict control over process-related impurities.
Solid Oral Dosage Formulation Development: Optimized particle size distribution allows seamless direct compression or wet granulation manufacturing, featuring exceptional powder flow characteristics that reduce tablet weight variation during high-speed rotary press operations.
FAQ
Q: What is the regulatory filing status of this API?
A: A comprehensive Drug Master File is available, supporting regulatory submissions across multiple regional jurisdictions.
Q: How is batch-to-batch consistency maintained during commercial production?
A: Production utilizes validated automated parameter controls across reaction, crystallization, and drying stages, supported by rigorous in-process quality testing.
Q: Can particle size distribution be customized for specific formulation requirements?
A: Yes, micronization parameters can be adjusted via jet milling to meet target particle size distributions such as d90 < 20 µm.
Q: What stability testing data is available for review
A: Long-term (25°C / 60% RH) and accelerated (40°C / 75% RH) stability data packages are maintained in compliance with applicable guidelines.
Q: Are reference analytical standards provided for method transfer?
A: Well-characterized working standards accompanied by complete analytical dossiers are available upon request to facilitate method validation in customer laboratories.
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