Isolation and characterization of major degradants in dihydroergotamine injection

• Autorzy: Basappa Praveen , Uma Shankar MS , Dama Venugopala Rao

Identyfikatory

DOI

10.1556/1326.2022.01095

• Języki publikacji: EN

Abstrakty

EN

In this study, we report the systematic approach for characterization of two major degradant impurities, which are not listed in any compendia and were formed during the stability studies of Dihydroergotamine mesylate injection (DHE). An ion-pair UPLC chromatographic method was developed to quantify the related substances present in the DHE injection drug product. The same was used to monitor the impurity profiling during its stability. The two unknown impurities were observed at RRT about 0.08 (Impurity-1) and RRT about 0.80 (Impurity-5) and found to be significantly increasing on stability. Forced degradation studies revealed the nature of the impurity and conditions required for enriching them. A Mass compatible HPLC method was developed to quantify only these two impurities using 25% ammonia and formic acid in water. Their mass numbers were identified using LC MS/MS with triple quadruple mass spectrometer coupled with a HPLC. These two impurities were then isolated from enriched products using preparative HPLC. These impurities were then characterized using Mass and NMR analysis along with Q-TOF elemental analysis.

Słowa kluczowe

EN

dihydroergotamine mesylate injection; impurity isolation; impurity characterization

• Wydawca: University of Silesia in Katowice ; Akademiai Kiado
• Czasopismo: Acta Chromatographica
• Rocznik: 2024
• Tom: Vol. 36, no. 2
• Strony: 86–98
• Opis fizyczny: Bibliogr. 14 poz., rys., wykr.

Twórcy

autor

Basappa Praveen

• Integrated Product Development, Dr Reddys Laboratory, Bachupally, Hyderabad, Telangana-500049, India

autor

Uma Shankar MS

• Department of Pharmaceutics, SRM University, Kattankulathur, Chengalpattu District, Tamil Nadu–603203, India

• https://orcid.org/0000-0002-2762-6148

autor

Dama Venugopala Rao

• Integrated Product Development, Dr Reddys Laboratory, Bachupally, Hyderabad, Telangana-500049, India

Bibliografia

• 1. Russell, M. B. Is migraine a genetic illness? The various forms of migraine share a common genetic cause. Neurol. Sci. 2008 May, 29(Suppl 1). https://doi.org/10.1007/s10072-008-0887-4, 18545897.
• 2. Sprenger, T.; Goadsby, P. J. Migraine pathogenesis and state of pharmacological treatment options. BMC Med. 2009 Nov 16, 7(1), 1–5.
• 3. The pharmacology of ergotamine and dihydroergotamine -PubMed [Internet]. [cited 2021 Nov 5]. Available from: https://pubmed.ncbi.nlm.nih.gov/9009470/.
• 4. Fda, Cder. Label.
• 5. USP monographs: dihydroergotamine mesylate [Internet]. [Cite 2021 Nov 5]. Available from: http://www.pharmacopeia.cn/v29240/usp29nf24s0_m26080.html.
• 6. ICH Q3B (R2) impurities in new drug products | European medicines agency [Internet]. [cited 2021 Nov 5]. Available from: https://www.ema.europa.eu/en/ich-q3b-r2-impurities-new-drug-products.
• 7. ICH topic Q 1 A (R2) stability testing of new drug substances and products step 5 note for guidance on stability testing: stability testing of new drug substances and products. 2003.
• 8. Vuyyuru, N. R.; Krishna, G. V.; Ramadevi, B.; Kumar, Y. R. Evaluation of process impurities and degradants of sitagliptin phosphate by validated stability indicating RP-LC method. Asian J. Chem. 2017, 29(9), 1941–7. https://doi.org/10.14233/ajchem.2017.20632.
• 9. Rajana, N.;Devi, D. R.;Kumar Reddy, D.N.; Babu, J. M.; Basavaiah,K.; Balakumaran, K. Characterization of five oxidative degradation impurities and one process impurity of suvorexant drug substance by LC-MS/MS, HR-MS and 1D, 2D NMR: validation of suvorexant drug substance and process impurities by HPLC and UPLC. J. Chromatogr. Sci. 2020 Apr 25, 58(5), 433–44.
• 10. Vuyyuru, N. R.; Reddy, A. M.; Ramadevi, B.; Kumar, Y. R.; Durga Prasad, B. J. A simple, specific, mass compatible and validated gas chromatographic method for theestimation of piperidine-3-amine content in linagliptin finished and stability samples without derivatization. Asian J. Chem. 2020, 32(10), 2567–72. https://doi.org/10.14233/ajchem.2020.22817.
• 11. Forced degradation as an integral part of HPLC stability-indicating method development [Internet]. [cited 2021 Nov 5]. Available from: https://www.researchgate.net/publication/280139268_Forced_degradation_as_an_integral_part_of_HPLC_stabilityindicating_method_development.
• 12. Smyth,W. F.; Joyce, C.; Ramachandran, V. N.; O’Kane, E.; Coulter, D. Characterisation of selected hypnotic drugs and their metabolites using electrospray ionisation with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by liquid chromatography-electrospray ionisation–i. Anal. Chim. Acta 2004 Mar 24, 506(2), 203–14.
• 13. Nagireddy, V.; Vamsikrishna, G.; Malati, V.; Ramadevi, B.; Ravindrakumar, Y. Chiral recognition of polysaccharide based CSP for separation of enantiomers and regio isomers of Prasugrel and its related impurities. J. App Pharm. Sci. 2017, 7(7), 218–24.
• 14. Raghunadha Babu, C. V.; Vuyyuru, N. R.; Padmaja Reddy, K.; Suryanarayana, M. V.; Mukkanti, K. Estimation of enantiomeric impurity in piperidin-3-amine by chiral HPLC with precolumn derivatization. Chirality 2014, 26(12), 775–9. https://doi.org/10.1002/chir.22352.