Name: Lapatinib ditosylate monohydrate
CAS Number: 388082-78-8
Chemical Formula: C₄₃H₄₄ClFN₄O₁₁S₃ (or written as C₂₉H₂₆ClFN₄O₄S·2C₇H₈O₃S·H₂O)
Molecular Weight 943.48 g/mol
ikB
InChI=1S/C29H26ClFN4O4S.2C7H8O3S.H2O/c1-40(36,37)12-11-32-16-23-7-10 -27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22 )38-17-19-3-2-4-21(31)13-19;21-6-2-4-7(5-3-6)11(8,9)10;/h2-10,13- 15,18,32H,11-12,16-17H2,1H3,(H,33,34,35);22-5H,1H3,(H,8,9,10);1H2
ikB Key XNRVGTHNYCNCFF-UHFFFAOYSA-N
Density 1.403 g/mL (20.84°C)
Boiling Point 750.7°C at 760 mmHg
Melting Point 236–259°C (decomposes)
Water Solubility Almost insoluble (0.007 mg/mL, 25°C)
Vapor Pressure Not reported
Refractive Index Not reported
Storage Conditions Store in a sealed container at -20°C, or protected from light at 4°C; for long-term storage, store in a cool, dry place.
Sensitivity Photosensitive; store protected from light.
Appearance White to pale yellow crystalline powder
Specific Gravity Approx. 1.40
Color White to pale yellow
BRN Not reported
MDL Number MFCD18904381 / MFCD21090418
Hazard Symbol GHS07 (exclamation mark)
Risk Terms H302 (Harmful if swallowed); H315 (Causes skin irritation); H319 (Causes severe eye irritation); H335 (May cause respiratory irritation)
Safety Terms: P264 (Wash thoroughly after handling); P280 (Wear protective gloves/eye protection); P301+P312 (If swallowed, immediately call a poison control center/doctor); P302+P352 (If in contact with skin, rinse with plenty of water); P304+P340 (If inhaled, move to fresh air); P305+P351+P338 (If in eyes, rinse carefully with water)
Customs Code: 2934999099 (China)
II. Properties: Lapatinib ditosylate monohydrate is a highly effective dual-target tyrosine kinase inhibitor that simultaneously targets and inhibits the intracellular tyrosine kinase domains of epidermal growth factor receptor (EGFR/HER1/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2). Its IC₅₀ value for purified EGFR was 10.8 nM, for ErbB2 it was 9.2 nM, and for ErbB4 it was 367 nM, exhibiting high target selectivity.
This compound is a yellow solid, belonging to the quinazoline derivative class. Its chemical structure contains a quinazoline core, a fluorobenzyloxy group, and key pharmacophores such as furanylmethylsulfonyl ethylamino. Its salt form is a ditosylate salt with one molecule of water of crystallization, significantly improving the solubility of the free base and formulation stability.
In in vitro cell experiments, lapatinib effectively inhibited EGFR and HER2 receptor autophosphorylation at low nanomolar concentrations, blocking downstream AKT and MAPK signaling pathways, thereby inducing G1 phase arrest in tumor cells and inhibiting cell proliferation. In animal models, oral administration (30–100 mg/kg, twice daily) significantly inhibited the growth of xenograft tumors such as BT474 and HN5. Furthermore, this compound retained significant activity against trastuzumab-resistant breast cancer cell lines, suggesting no cross-resistance with trastuzumab.
III. Uses
Anti-tumor drug active pharmaceutical ingredient (API): As the active pharmaceutical ingredient (API) of the targeted anti-tumor drug lapatinib, it is primarily used to treat HER2-positive advanced or metastatic breast cancer, often in combination with capecitabine. It can also be used for investigational treatment of EGFR-overexpressing solid tumors (such as lung cancer and head and neck cancer).
Research reagent:** Widely used in molecular biology, cell biology, and tumor signaling pathway research. As a standard positive control compound for EGFR/HER2 inhibitors, it is used to explore the mechanisms of action of receptor tyrosine kinases in tumorigenesis, angiogenesis, apoptosis, and autophagy.
Drug formulation development:Used for pre-formulation studies and process development of oral solid dosage forms such as tablets and capsules. The original drug Tykerb/Tyverb (250 mg, calculated as lapatinib free base) uses this product as the API, with each tablet containing 405 mg of this product.
Combination Therapy Studies: In in vitro and in vivo studies, this product, when used in combination with drugs such as 5-fluorouracil, vinorelbine, and trastuzumab, exhibits a synergistic antitumor effect, providing experimental evidence for clinical combination therapy regimens.
IV. Preparation Method: This product is prepared using a multi-step organic synthesis and salt-forming crystallization process. The main synthetic route is as follows:
Step 1: Construction of the Quinazoline Core: Starting with 4-chloro-6-nitroquinazoline, a nucleophilic substitution reaction is carried out with 3-chloro-4-(3-fluorobenzyloxy) to introduce a key side chain, yielding the N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-nitroquinazoline-4-amine intermediate.
Step 2: Nitro Reduction and Furan Side Chain Introduction: After reducing the nitro group to an amino group, a 5-formylfuran-2- group is introduced at the 6-position through diazotization or nucleophilic substitution. Subsequently, it undergoes a reductive amination reaction with N-(2-methylsulfonylethyl)amine to construct the complete lapatinib free base structure (C₂₉H₂₆ClFN₄O₄S).
Step 3: Salt Formation and Crystallization
The lapatinib free base is dissolved in a suitable organic solvent and reacted with two equivalents of p-toluenesulfonic acid to form di-p-toluenesulfonate. By precisely controlling the crystallization conditions (solvent system, temperature gradient, stirring rate), one molecule of water of crystallization is introduced to obtain a stable monohydrate crystal form. This crystal form exhibits good polymorphic stability, suitable solubility, and excellent chemical stability, meeting pharmaceutical standards.
Quality Control: Each batch of product undergoes HPLC (purity ≥99.0%), LC-MS (molecular weight confirmation), XRD (crystal form identification), KF (moisture content 1.5–2.5%), residual solvent, and heavy metal testing to ensure compliance with USP/EP standards.
V. Safety Information
GHS Hazard Categories: Acute toxicity (oral, Category 4); Skin corrosion/irritation (Category 2); Serious eye damage/irritation (Category 2A); Specific target organ toxicity—single exposure, respiratory irritation (Category 3).
Handling Protection: Operators should wear protective gloves, safety glasses, and dust masks. Weighing and dispensing operations should be performed in a fume hood to avoid inhalation of dust or contact with skin and eyes.
First Aid Measures: If swallowed, rinse mouth immediately and seek medical attention; if contact with skin, wash with plenty of soap and water; if splashed into eyes, flush with running water for at least 15 minutes and seek medical attention; if inhaled, move to fresh air and perform artificial respiration if necessary.
Fire-fighting Measures: This product is a flammable solid and may produce toxic nitrogen oxides, sulfur oxides, hydrogen fluoride, and hydrogen chloride gases upon contact with fire. Dry powder, carbon dioxide, or foam fire extinguishers can be used for extinguishing.
Spill Handling: Wear personal protective equipment, collect the spilled material with an inert absorbent material (such as diatomaceous earth), place it in a sealed container, and treat it as hazardous waste. Avoid flushing it into the sewer system.
Disposal: Dispose of it as hazardous chemical waste according to local regulations. It is recommended to have it incinerated by a qualified hazardous waste treatment facility.
VI. Our Production Advantages and Capacity
As a high-tech enterprise specializing in the R&D and production of anti-tumor active pharmaceutical ingredients and advanced pharmaceutical intermediates, our company possesses the following core advantages in the production of lapatinib ditosylate monohydrate:
1. Synthesis Process Advantages
We possess an optimized synthesis route with independent intellectual property rights, increasing the overall yield by more than 15% compared to traditional processes, significantly reducing production costs.
We employ continuous flow reaction technology for the key nitration-reduction reaction steps, resulting in high reaction selectivity and excellent impurity control, with single impurities controlled below 0.1%.
The salt crystallization section utilizes an advanced programmed temperature-controlled crystallization system, ensuring uniform crystal form and good flowability of the product, directly meeting the requirements of the tableting process.
2. Quality Control Advantages
Equipped with a full range of analytical instruments including UPLC-MS, NMR, XRD, DSC, and TGA, and has established a complete impurity profile research database (≥12 known impurities).
Strictly adheres to ICH Q3A/Q3C guidelines, providing detailed COA (Certificate of Assessment), MSDS (Material Safety Data Sheet), and MoA (Method of Analysis) for each batch.
ISO 9001 quality management system certified, currently undergoing GMP compliance audit, and can support clients’ ANDA/NDA applications.
3. Registration and Compliance Advantages
Provides complete DMF (Drug Master File) technical support to assist clients in completing drug registration applications in Europe, the US, and China.
Established a comprehensive traceability system, achieving full-chain batch record management from starting materials to finished products, meeting the stringent traceability requirements of regulatory agencies for active pharmaceutical ingredients.
4. Production Capacity and Supply Advantages
Existing capacity: 500 kg/year of lapatinib ditosylate monohydrate, with the potential to rapidly expand to 2 tons/year based on market demand.
Delivery Time: 2-3 weeks for regular orders; 4-6 weeks for bulk orders (≥100 kg).
Packaging Specifications: Available in various packaging sizes including 1 g, 10 g, 100 g, 1 kg, 5 kg, and 25 kg, with double-layered PE bags inside and aluminum foil bags or cardboard drums outside, meeting the needs of all stages from laboratory R&D to commercial production.
Global Logistics: Supports ambient/cold chain transportation, equipped with temperature-controlled recorders to ensure stable product quality during transportation.
5. Technical Service Advantages: Provides customized synthesis services from milligram to ton scale, supporting clients in salt form screening, crystal form research, and pre-formulation development.
A professional technical team provides 24/7 technical consultation to assist clients in resolving issues related to formulation compatibility, stability studies, and analytical method transfer.
Keywords: Lapatinib ditosylate monohydrate, CAS 388082-78-8, HER2 inhibitor, EGFR inhibitor, tyrosine kinase inhibitor, antitumor API, breast cancer raw material, GW572016, Tykerb, Tyverb, quinazoline kinase inhibitor, lapatinib ditosylate monohydrate manufacturer, high-purity lapatinib raw material.
Post time: Jun-09-2026
