LC-MS/MS STUDY OF THE TRACE LEVEL IMPURITIES OF IRBESARTAN AN ANGIOTENSIN II RECEPTOR ANTAGONIST MOLECULE TO ITS ORIGIN THROUGH nMS2 TECHNIQUE
Objective: The mass characterization of five trace level related impurities of Irbesartan was performed through the â€œnMS2â€ technique of triple quadrupole mass spectrometer and also to Correlated to the impurity origin.
Methods: A simple & effective patented process was applied to get the impurity profile, and mass characterization was performed through the â€œnMS2â€ technique of triple quadrupole mass spectrometer analyser.
Results: The simple production scan in differential collision energies is coined as â€œnMS2â€ technique of the triple quadrupole analyzer. The molecular ion fragmentation occurs with multiple collision energies and provides meaningful MSMS fragments for characterizing five trace level impurities less than 0.5% of angiotensin II receptor antagonist-Irbesartan. The origin of the impurity formation in the synthetic process was successfully related to the Spiro ketones.
Conclusion: The results obtained in this research clearly indicates the approach of â€œnMS2â€ technique was very useful in the identification and structural prediction of trace level related impurities of Irbesrtan.
2. S Ahuja. Assuring quality of drugs by monitoring impurities. Adv Drug Delivery Rev 2007;59:3-11.
3. RJ Smith, ML Webb. Analysis of drug impurities. Blackwell Publishing, Oxford, UK; 2007.
4. J Zheng. Formulation and analytical development for low-dose oral drug products. John Wiley and Sons, Inc, Hoboken, New Jersey; 2009. p. 25-38.
5. Akshatha HS, Gurupadayya BM. Application of liquid chromatography coupled with mass spectrometry in the impurity profiling of drug substances and products. Asain J Pharm Clin Res 2018;5:30-7.
6. S Gorog. Identification and determination of impurities in drugs Elsevier, Amsterdam; 2000.
7. SR Chemburkar, J Bauer. Dealing with the impact of ritonavir polymorphs on the late stages of bulk drug process development. Organic Process Res Development 2000;4:413-7.
8. KPR Chowdary, K Ravi Shankar, VVLSP Sowjanya. Optimization of irbesartan tablet formulation by 23 factorial design. Int J Curr Pharm Res 2015;7:39-42.
9. K Basak, HB Patel. Pharmaceutical impurities: a regulatory perspective for abbreviated new drug applications. Adv Drug Delivery Rev 2007;59:64-72.
10. D Annopkumar Anoop Kumar, Ganesh Darekar, Suma Ramagiri, Neha Bhasin, Manoj Pillai, Dev Kant Shandilya. Generic workflow using advanced analysis and data interpretation tools for identification of Irbesartan degradation products by liquid chromatography coupled to high-resolution mass spectrometry. Anal Chem Indian J 2015;15:352-63.
11. Somisetti Narender Rao, Devarasetty Sitaramaih, Challa Nageswar Rao, Peddi Srinivasa Rao, K Sudhakar Babu. Commercial scalable process for the preparation of irbesartan intermediate. Rasayan J Chem 2010;3:681-9.
12. Lars Peters, Roland Fr?hlich, Alan SF Boyd, Arno Kraft. Tetrazole binding to amidine bases, Fifth International Electronic Conference on Synthetic Organic Chemistry; 2004.
13. Stanislav Radl, Jan Stach, Jaroslav Havlicek, Marcela Tkadlecova, Lukas Placek. Synthesis and identification of some impurities of Irbesartan. Acta Chim Slov 2009;56:559-65.
14. US. Pharmacopoeia USP30-NF25, Irbesartan (CAS: 138402-11-6); 2018.