ItemArticle

Synthesis, impurity profiling, simultaneous NP-HPTLC method development, molecular modelling study and EGFR tyrosine kinase inhibitory profile: An integrated approach to characterize desethynyl erlotinib process impurity

Title
Synthesis, impurity profiling, simultaneous NP-HPTLC method development, molecular modelling study and EGFR tyrosine kinase inhibitory profile: An integrated approach to characterize desethynyl erlotinib process impurity
Creator
Bhadane, Kunal; Patil, Bhatu; Chinnam, Sampath; Das, Biswajit; Patil, Chandragouda; Gawli, Chandrakant; Ahmad, Iqrar; Shimpi, Amit; Agrawal, Yogesh; Patil, Amod; Shirkhedkar, Atul; Rai, Nishant; Palkar, Mahesh; Ansari, Siddique Akber; Ansari, Irfan Aamer; Kundu, Chanakya Nath; Patel, Harun
Description
The study presents an integrated approach to characterizing Desethynyl Erlotinib, a process impurity in the synthesis of Erlotinib, a potent EGFR tyrosine kinase (EGFR TK) inhibitor used in lung cancer treatment. A normal phase high-performance thin-layer chromatography (NP-HPTLC) method was developed and validated for the simultaneous profiling of Erlotinib and its Desethynyl Erlotinib impurity. The optimized method utilized ethyl acetate, methanol, and glacial acetic acid (9: 0.5: 0.5 v/v/v) as the mobile phase for effective separation and quantification. The method demonstrated excellent linearity for Erlotinib and its impurity over a concentration range of 200-1200 ng/spot, with R2 values of 0.9979 and 0.9998, respectively. Validation confirmed precision with intra-day and inter-day % RSD values of less than 2% and robustness. The limits of detection (LOD) and quantification (LOQ) were 5.18 ng/spot and 15.70 ng/spot for Erlotinib and 7.07 ng/spot and 21.43 ng/spot for the impurity. In-vitro assays against the A549 lung cancer cell line expressing wild-type EGFR tyrosine kinase (WT EGFR TK) showed that the Desethynyl Erlotinib impurity exhibits significant inhibition compared to Erlotinib, suggesting the potential toxicity of the Desethynyl Erlotinib impurity and causing side effects such as diarrhea, skin rashes and interstitial lung disease due to WT EGFR tyrosine kinase (WT EGFR TK) inhibition. Molecular docking and molecular dynamics simulations further corroborated greater stability in the Desethynyl Erlotinib impurity with WT EGFR tyrosine kinase (WT EGFR TK). Clinically, these findings highlight the importance of monitoring and minimizing impurities like Desethynyl Erlotinib to prevent adverse effects and maintain the therapeutic safety of Erlotinib in lung cancer treatment. This research underscores the necessity for rigorous quality control in Erlotinib production to ensure purity and therapeutic effectiveness. 2025 Har Krishan Bhalla & Sons.
Source
Analytical Chemistry Letters;Volume;15;Issue;1;pp.47-64
Date
01-01-2025
Publisher
Taylor and Francis Ltd.
Subject
Desethynyl Erlotinib impurity; Docking; Erlotinib; High Performance Thin Layer Chromatography; Wild Type EGFR Tyrosine Kinase
Coverage
Bhadane K., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Patil B., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Chinnam S., Department of Chemistry, M.S. Ramaiah Institute of Technology (Autonomous Institute, Affiliated to Visvesvaraya Technological University, Belgaum), Karnataka, Bengaluru, 560054, India; Das B., Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Campus-11, Bhubaneswar, Odisha, Patia, 751024, India; Patil C., Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Gawli C., Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Ahmad I., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Shimpi A., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Agrawal Y., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Patil A., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Shirkhedkar A., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India; Rai N., Department of Pharmaceutical Chemistry, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKMs NMIMS, V.L. Mehta Road Vile Parle (W), Mumbai, 400056, India, Graphic Era (Deemed to be University)-Clement Town, Uttarakhand, Dehradun, 248002, India; Palkar M., Department of Pharmaceutical Chemistry, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKMs NMIMS, V.L. Mehta Road Vile Parle (W), Mumbai, 400056, India; Ansari S.A., Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; Ansari I.A., Department of Drug Science and Technology, University of Turin, Turin, 10124, Italy; Kundu C.N., Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Campus-11, Bhubaneswar, Odisha, Patia, 751024, India; Patel H., Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India
Rights
Restricted Access; Hardcopy may be available in the library
Relation
ISSN: 22297928;
Format
online
Language
English
Type
Article

Citation

Bhadane, Kunal; Patil, Bhatu; Chinnam, Sampath; Das, Biswajit; Patil, Chandragouda; Gawli, Chandrakant; Ahmad, Iqrar; Shimpi, Amit; Agrawal, Yogesh; Patil, Amod; Shirkhedkar, Atul; Rai, Nishant; Palkar, Mahesh; Ansari, Siddique Akber; Ansari, Irfan Aamer; Kundu, Chanakya Nath; Patel, Harun, “Synthesis, impurity profiling, simultaneous NP-HPTLC method development, molecular modelling study and EGFR tyrosine kinase inhibitory profile: An integrated approach to characterize desethynyl erlotinib process impurity,” CHRIST (Deemed To Be University) Institutional Repository, accessed June 19, 2026, https://archives.christuniversity.in/items/show/22776.

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