Tepotinib API Manufacturer in India

Swapnroop Pharma · WHO-GMP Certified · +91 87670 62101

Tepotinib is an orally active, selective MET tyrosine kinase inhibitor (TKI) used in oncology. The pharmaceutical product TEPMETKO contains tepotinib hydrochloride hydrate, while the active moiety is tepotinib. Tepotinib selectively inhibits MET signaling, including signaling associated with MET exon 14 skipping alterations, which can drive tumor-cell proliferation, survival, migration and invasion.

The free-form tepotinib has the molecular formula C29H28N6O2 and molecular weight 492.58 g/mol. Its pharmaceutical form, tepotinib hydrochloride hydrate, has the formula C29H28N6O2·HCl·H2O and molecular weight 547.05 g/mol. The FDA label identifies the hydrochloride hydrate as the material used in TEPMETKO.

For your product page, I recommend using Tepotinib Hydrochloride Hydrate in the Product Data section rather than treating 492.58 g/mol as the molecular weight of the marketed API form.

API IDENTIFICATION

ParameterValue
Product NameTepotinib
Pharmaceutical FormTepotinib Hydrochloride Hydrate
CAS No.1946826-82-9
Free-Base CAS1100598-32-0
FDA UNIIVY5YX2TQ1F
Development CodeMSC2156119 / EMD-1214063
Molecular Formula – Free BaseC29H28N6O2
Molecular Weight – Free Base492.58 g/mol
Molecular Formula – HCl HydrateC29H28N6O2·HCl·H2O
Molecular Weight – HCl Hydrate547.05 g/mol
Therapeutic ClassAntineoplastic
Drug ClassMET Tyrosine Kinase Inhibitor
TargetMET / c-MET
Physical FormWhite to off-white powder

FDA and DailyMed identify tepotinib hydrochloride hydrate as the pharmaceutical drug substance used in TEPMETKO.

PubChem identifies CAS 1946826-82-9 for the hydrochloride hydrate and CAS 1100598-32-0 for the anhydrous hydrochloride/free-form records.

CHEMICAL & PHARMACEUTICAL PROFILE

Tepotinib is a small-molecule kinase inhibitor designed to selectively inhibit the mesenchymal-epithelial transition factor (MET) receptor tyrosine kinase.

The free base has a molecular weight of 492.58 g/mol, while the pharmaceutical hydrochloride hydrate has a molecular weight of 547.05 g/mol. The difference is important when calculating assay basis, formulation equivalence and API quantity.

Tepotinib hydrochloride hydrate is described as a white to off-white powder and has a reported pKa of 9.5. It is a low-solubility compound with strongly pH-dependent solubility.

The pharmaceutical substance is non-hygroscopic according to the product information reviewed by EMA and other regulatory documentation.

MECHANISM OF ACTION

Tepotinib selectively targets the MET receptor tyrosine kinase.

MET can be activated by hepatocyte growth factor (HGF), leading to downstream signaling pathways that regulate cell proliferation, survival, migration and invasion. Tepotinib inhibits both HGF-dependent and HGF-independent MET phosphorylation and suppresses MET-dependent downstream signaling.

This mechanism is particularly relevant to tumors carrying MET exon 14 skipping alterations, in which abnormal MET signaling can promote oncogenic activity.

PHARMACEUTICAL APPLICATIONS

Tepotinib API is used in the manufacture of oncology medicines intended for MET-driven cancers.

Its principal pharmaceutical application is:

  • MET exon 14 skipping alteration-positive non-small cell lung cancer (NSCLC)
  • Advanced or metastatic NSCLC with an appropriate MET alteration
  • MET-driven solid-tumor research and pharmaceutical development

The FDA-approved TEPMETKO indication is for adults with metastatic NSCLC whose tumors have MET exon 14 skipping alterations.

QUALITY & ANALYTICAL TESTING

Tepotinib hydrochloride hydrate is a chemically synthesized small-molecule API and should be characterized using a comprehensive pharmaceutical analytical package.

Appropriate controls can include:

  • Identification by IR
  • HPLC identification
  • HPLC assay
  • Related substances by HPLC
  • Residual solvents by GC
  • Water content by Karl Fischer
  • Solid-state characterization
  • PXRD
  • Elemental/inorganic impurities
  • Chloride content where applicable
  • Assay on appropriate chemical-form basis
  • Particle-size characterization where required

The exact numerical acceptance criteria should come from the applicable approved drug-substance specification. I could not verify a public universal BP/Ph. Eur./USP monograph containing the complete numerical release limits for tepotinib hydrochloride hydrate, so those fields should not be populated with invented numbers.

MANUFACTURING

Tepotinib is a synthetic small-molecule pharmaceutical API. Manufacturing involves controlled chemical synthesis, purification and isolation of the required pharmaceutical form.

For a commercial API manufacturing process, important quality attributes include:

  • Chemical identity
  • Assay
  • Related substances
  • Residual solvents
  • Water content
  • Solid-state form
  • Polymorphic/hydrate control
  • Particle-size distribution
  • Elemental impurities
  • Batch consistency

Because the approved pharmaceutical substance is specifically tepotinib hydrochloride hydrate, control of hydration state and solid form is particularly important.

The pKa and pharmaceutical-form data are supported by FDA labeling and product information; the calculated XLogP3-AA and TPSA are from PubChem.

SOLUBILITY

Tepotinib has pH-dependent aqueous solubility.

Regulatory documentation describes tepotinib as:

  • Slightly soluble at approximately pH 4.5
  • Practically insoluble at pH 1.2
  • Practically insoluble at pH 7.4
  • Practically insoluble in simulated gastric fluid
  • Solubility decreases in the presence of chloride ions

 

Therefore, I recommend entering “pH-dependent solubility” in the CMS Solubility field rather than using an unsupported single mg/mL number.

PACKAGING & STORAGE

Tepotinib API should be stored in an appropriate pharmaceutical-grade container that protects the material from contamination and environmental exposure.

The finished TEPMETKO product is stored at 20–25°C, with permitted excursions between 15–30°C. This is a finished-product storage condition and should not automatically be treated as the API storage specification.

For bulk API, the manufacturer's validated stability program should determine the:

  • Storage temperature
  • Container-closure system
  • Retest period
  • Moisture protection
  • Light protection
  • Shipping conditions

DOCUMENTATION

A pharmaceutical Tepotinib API manufacturer should maintain appropriate documentation including:

  • Certificate of Analysis (CoA)
  • Product specification
  • Batch analytical report
  • HPLC assay and purity data
  • Related-substance profile
  • Residual-solvent data
  • Water-content data
  • Solid-state/PXRD data where applicable
  • Stability data
  • Packaging information
  • Safety Data Sheet (SDS)
  • Regulatory support documentation

WHY CHOOSE TEPOTINIB API MANUFACTURER IN INDIA?

Tepotinib is a specialized oncology API requiring control of chemical purity, related substances, solid-state characteristics and the correct hydrochloride hydrate form.

A qualified Tepotinib API manufacturer in India should maintain validated analytical methods, controlled chemical synthesis, appropriate impurity controls and consistent batch quality.

For pharmaceutical customers, it is particularly important to confirm whether the required material is tepotinib free base, tepotinib hydrochloride anhydrous or tepotinib hydrochloride hydrate, because these forms have different molecular formulas and molecular weights.

Detailed Specifications

Parameter Specification
Appearance white to off-white crystalline powder
Identification IR & HPLC compliant
Assay (HPLC) 98.0% – 102.0%
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