Osimertinib Mesylate is a third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor engineered to selectively target activating and T790M resistance mutations while preserving wild-type receptor profiles. Manufactured via validated synthetic pathways that ensure high chiral purity, this active pharmaceutical ingredient serves as the core constituent for oral solid dosage forms designed for targeted oncology treatments.
Technical Parameters
|
Parameter |
Specification Detail |
|
International Nonproprietary Name |
Osimertinib Mesylate |
|
CAS Number |
1421373-66-1 |
|
Molecular Formula |
C28H33N7O2 · CH4O3S |
|
Molecular Weight |
599.71 g/mol |
|
Structural Class |
Aminopyrimidine derivative / Kinase inhibitor |
|
Appearance |
White to off-white crystalline powder |
|
Solubility |
Practically insoluble in water; sparingly soluble in polar organic solvents |
|
Storage Conditions |
Store in tightly closed containers below 25°C, protected from light and moisture |
|
Shelf Life |
36 months under designated storage conditions |
Quality and Analytical Specifications
Identification: Conforms to reference standard via Infrared Absorption and HPLC retention time.
Assay: 98.5% to 101.5% calculated on an anhydrous basis via High-Performance Liquid Chromatography.
Chiral Purity: Enantiomeric excess greater than or equal to 99.5% via chiral chromatography.
Impurities Profile: Individual specified impurities limited to 0.10% maximum; total impurities capped at 0.50%.
Residual Solvents: Complies with ICH Q3C limits verified through headspace gas chromatography.
Water Content: Maximum 1.0% determined by volumetric Karl Fischer titration.
Residue on Ignition: Maximum 0.1% via gravimetric analysis.
Heavy Metals: Maximum 20 ppm measured by inductively coupled plasma mass spectrometry.
Particle Size Distribution: Controlled parameter (D90 below 50 µm), adjustable to client formulation requirements.
Manufacturing and Quality Assurance
Production Environment: Commercial-scale multi-purpose synthesis executed within closed-system processing lines and ISO Class 8 cleanrooms.
Purification and Isolation: Multi-step organic synthesis incorporating catalytic hydrogenation, controlled crystallization, and centrifugal filtration to isolate defined polymorphic forms.
Containment Standards: High-containment isolators utilized during isolation, drying, and micronization to ensure containment and operator safety.
Supply Chain Integrity: Validated dual-sourcing for raw materials paired with maintained safety stock of intermediate compounds to ensure continuous delivery schedules.
Documentation and Regulatory Support
Regulatory Filings: Drug Master File compiled in ICH format ready for global regulatory submission.
Lot Certification: Comprehensive Certificate of Analysis supplied with every commercial batch, detailing full chromatographic impurity charts.
Compliance Packages: Good Manufacturing Practice compliance statements, stability study summaries covering accelerated and long-term data, and absence statements for transmissible spongiform encephalopathy.
Safety Documentation: Material Safety Data Sheet detailing toxicological parameters, personal protective equipment requirements, and handling protocols.
Packaging and Logistics
Primary Packaging: Food-grade, double-layer low-density polyethylene bags heat-sealed under positive pressure nitrogen purge.
Secondary Packaging: Rigid fiber drums or aluminum-laminated protective canisters providing puncture resistance and light shielding.
Moisture Control: Pharmaceutical-grade silica gel desiccant packets integrated between primary and secondary liners.
Labeling Standards: Barcoded lot identification tags displaying CAS number, net weight, gross weight, storage specifications, re-test date, and facility designation.
Pharmaceutical Applications
Oncology Formulations: Active pharmaceutical ingredient deployed in oral medications targeting locally advanced or metastatic non-small cell lung cancer with EGFR T790M mutations.
First-Line Regimens: Incorporated into daily oral tablet therapies for patients possessing activating exon 19 deletions or exon 21 L858R substitutions.
Adjuvant Protocols: Utilized in post-surgical maintenance dosing regimens for stage IB to IIIA patient cohorts.
Tableting Efficiency: Optimized powder flowability and compressibility characteristics supporting direct blending or wet granulation manufacturing processes.
FAQ
Q: What is the current regulatory status of the Drug Master File?
A: A comprehensive master file is maintained in ICH format, available for reference authorization upon formal request.
Q: Which polymorphic form is delivered in commercial shipments?
A: The active ingredient is supplied as a thermodynamically stable crystalline form verified via X-ray powder diffraction and differential scanning calorimetry.
Q: How are genotoxic impurities managed?
A: All potential process-related residuals are monitored via validated liquid chromatography-tandem mass spectrometry methods and maintained below threshold limits in compliance with international guidelines.
Q: What are the available sample sizes for evaluation?
A: Evaluation sample quantities start at 100g for analytical testing, with commercial orders supplied in standard 5kg or 25kg drum configurations.
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