Separation, Identification, and Characterization of Degradation Products of Erlotinib Hydrochloride Under ICH-Recommended Stress Conditions by LC, LC-MS/TOF

Abstract

The present research work was carried out to determine the stability of erlotinib hydrochloride (ERLO) drug under different stress conditions recommended by International Conference on Harmonization (ICH) guideline Q1A (R2). The stability of the drug was studied under hydrolytic, oxidative, photolytic, and thermal stress conditions. The drug was found susceptible to degradation under acidic, basic, and photolytic stress conditions, while it was stable under neutral, oxidative, and thermal stress conditions. A total of three degradation products (DPs) were formed. Separation was carried out by using high-performance liquid chromatography system (HPLC). Better separation was achieved on Kromasil®(150 mm × 4.6 mm, 5 µm) C18 column using gradient elution program. A mixture of stressed samples was subjected to LC-MS/TOF studies to obtain mass spectral data. The information obtained from accurate mass study was first utilized to build a complete mass fragmentation pathway of the drug, and later it was used for its degradants. Structures were proposed for each fragment based on the best possible molecular formula. Three novel DPs 6-(2-hydroxyethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine, 6,7-bis(2-methoxyethoxy)quinazolin-4-amine, and N-(3-ethynylphenyl)-6, 7-bis (2-methoxyethoxy)-2-oxy-quinazolin-4-amine were identified.

Keywords:

• degradation pathway
• characterization
• erlotinib hydrochloride
• LC-MS/TOF
• stability indicating method
• stress study

Acknowledgments

The author would like to extend heartfelt thanks to Prof. Sarnajit Singh and Mrs. Parul Sharma, Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, S.A.S Nagar Mohali, Punjab, India, for their help in doing LC-MS/TOF studies and helpful guidance.