General Information

Afatinib Impurities and Afatinib 

Daicel Pharma synthesizes high-quality Afatinib impurities like 2-Hydroxy 3-dimethylamino Afatinib Impurity, 4-Hydroxy 4-Dedimethylamino Afatinib, Afatinib Bis-dimethylamino Impurity, Afatinib Impurity B, Afatinib Impurity E, and N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)-3-hydroxybutanamide, which are crucial in the analysis of the quality, stability, and biological safety of the active pharmaceutical ingredient Afatinib. Moreover, Daicel Pharma offers custom synthesis of Afatinib impurities and delivers them globally.

Afatinib [CAS: 850140-72-6] is a medicine of the anilino-quinazoline derivative class of drugs. It inhibits the activity of receptor tyrosine kinases (RTKs) known as the epidermal growth factor receptor (EGFR) family and has antineoplastic activity. Afatinib treats certain types of metastatic non-small cell lung cancer.

Afatinib: Use and Commercial Availability  

Afatinib is a medicine that targets and inhibits the ErbB family of tyrosine kinases irreversibly. The FDA has approved its use as a first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) with non-resistant epidermal growth factor receptor (EGFR) mutations. Additionally, it acts as a second-line treatment for advanced squamous non-small cell lung cancer (NSCLC). Gilotrif is the trade name for Afatinib.

Afatinib Structure and Mechanism of Action

The chemical name of Afatinib is (2E)-N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-2-butenamide. Its chemical formula is C₂₄H₂₅ClFN₅O_3, and its molecular weight is approximately 485.9 g/mol.

Afatinib binds to kinase domains, EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4). It inhibits tyrosine kinase autophosphorylation leading to the down-regulation of ErbB signaling.

Afatinib Impurities and Their Synthesis

During synthesis, storage, and use of Afatinib, impurities may arise, including organic impurities, such as intermediates, starting materials and potential genotoxic impurities, and inorganic impurities. Their presence compromises the safety and efficacy of the medication, making it crucial to control them. Strict quality control measures such as regular monitoring and testing are necessary to detect and manage Afatinib impurities.

Daicel provides a Certificate of Analysis (CoA) for Afatinib impurity standards, including 2-Hydroxy 3-dimethylamino Afatinib Impurity, 4-Hydroxy 4-Dedimethylamino Afatinib, Afatinib Bis-dimethylamino Impurity, Afatinib Impurity B, Afatinib Impurity E, and N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)-3-hydroxybutanamide. The CoA is issued from a cGMP-compliant analytical facility and contains complete characterization data, such as 1H NMR, 13C NMR, IR, MASS, and HPLC purity². Additional characterization data, such as 13C-DEPT and CHN, can be provided upon request. Daicel can also prepare any unknown Afatinib impurity or degradation product and offer labeled compounds to quantify the efficacy of Afatinib. Daicel offers Afatinib-D6, a deuterium-labeled Afatinib standard used in bio-analytical research such as BA/BE studies. We give a complete characterization report on delivery.