STABILITY INDICATING METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS QUANTIFICATION OF SORAFENIB AND REGORAFENIB DRUG SUBTANCES BY USING RP-UPLC

  • VIDYASAGAR CHOPPELLA Department of Engineering Chemistry, Andhra University College of Engineering (A), Andhra University, Visakhapatnam, Andhra Pradesh, India
  • RAGHU BABU K. Department of Engineering Chemistry, Andhra University College of Engineering (A), Andhra University, Visakhapatnam, Andhra Pradesh, India
  • SURESH BADIPATI Department of Engineering Chemistry, Andhra University College of Engineering (A), Andhra University, Visakhapatnam, Andhra Pradesh, India
  • HARITHA GONTHINA Department of Engineering Chemistry, Andhra University College of Engineering (A), Andhra University, Visakhapatnam, Andhra Pradesh, India
  • VENKATA KISHORE CHUKKA Department of Engineering Chemistry, Andhra University College of Engineering (A), Andhra University, Visakhapatnam, Andhra Pradesh, India

Abstract

Objective: The aim of the research work is to develop and validate a novel, sensitive, specific, rapid, accurate, precise and stability indicating gradient reverse phase ultra-performance liquid chromatography (RP-UPLC) method for the quantitative determination of sorafenib and regorafenib drug substances.


Methods: Liquid chromatographic method used for the analysis of the anti-cancer drug substances like sorafenib and regorafenib and method was developed and validated by using efficient chromatographic separation method and was achieved with the use of acquity UPLC system was used consisting of quaternary pump, photodiode array detector an auto injector and on line degasser.


Results: The separation was achieved using acquity UPLC BEH C18, 1.7 µm.2.1×50 mm analytical column at 30 °C employing a gradient elution. Empower software was used for data acquisition. During method validation all the parameters were evaluated as per ICH guidelines, which remained well within acceptable limits. Degradation of the drug substances was found to be stable to acidic, aqueous, basic hydrolysis, thermal hydrolysis and photolytic stress condition and the tests solution of the drug substance was found to be stable up to 24 h.


Conclusion: The results of linearity, precision accuracy and specificity were proved to be within the limits. This method can be employed in routine analysis for simultaneous estimation of sorafenib andregorafenib drug substances in quality formulations and dissolution studies.

Keywords: Regorafenib, Sorafenib, RP-UPLC

References

1. Anticancer drug; 2018. Available from: https://www.britannica.com/science/anticancer-drug. [Last accessed on 03 Dec 2019]
2. Hayden EC. Cutting off cancer's supply lines. Nature 2009;458:686–97.
3. Song T, Liang Y, Cao Z, Du W, Li Y. Computational analysis of specific micro RNA biomarkers for noninvasive early cancer detection. Hindawi Bio Med Res Int 2017;2017:1-9.
4. Corrie PG, Pippa G. Cytotoxic chemotherapy: clinical aspects. Medicine 2008;36:24–8.
5. Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharma Res 2008;25:2097–116.
6. Rampling R, James A, Papanastassiou V. The present and future management of malignant brain tumours: surgery, radiotherapy, chemotherapy. J Neurol Neurosurgery Psychiatry 2004;75 Suppl 2:24–30.
7. Kim S, Yazici YD, Calzada G, Wang ZY, Younes MN, Jasser SA, et al. Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Mol Cancer Ther 2007;6:1785-92.
8. Coriat R, Nicco C, Chereau C, Mir O, Alexandre J, Ropert S, et al. Sorafenib-induced hepatocellular carcinoma cell death depends on reactive oxygen species production in vitro and in vivo. Mol Cancer Ther 2012;11:2284-93.
9. Borthakur G, Kantarjian H, Ravandi F, Zhang W, Konopleva M, Wright JJ, et al. Phase I study of sorafenib in patients with refractory or relapsed acute leukemias. Haematologica 2011;96:62-8.
10. Huang L, Li G, Zhu J, Li Z, Li T, Leng X. Efficacy of sorafenib after liver transplantation in patients with primary hepatic carcinoma exceeding the Milan criteria: a preliminary study. Onco Targets Ther 2012;5:457–62.
11. Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, et al. A phase i dose–escalation study of regorafenib (BAY 73–4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res 2012;18:2658-67.
12. Crona DJ, Keisler MD, Walko CM. Regorafenib: a novel multitargeted tyrosine kinase inhibitor for colorectal cancer and gastrointestinal stromal tumors. Annals Pharmacother 2013;47:1685-96.
13. Strumberg D, Scheulen ME, Schultheis B, Richly H, Frost A, Buchert M, et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer 2012;106:1722–7.
14. Strumberg D, Schultheis B. Regorafenib for cancer. Expert Opin Invest Drugs 2012;21:879-89.
15. Tlemsani C, Huillard O, Arrondeau J, Pascaline BR, Cessot A, Blanchet B, et al. Effect of glucuronidation on transport and tissue accumulation of tyrosine kinase inhibitors: consequences for the clinical management of sorafenib and regorafenib. Expert Opin Drug Metab Toxicol 2015;11:785-94.
Statistics
85 Views | 109 Downloads
Citatons
How to Cite
CHOPPELLA, V., R. B. K., S. BADIPATI, H. GONTHINA, and V. K. CHUKKA. “STABILITY INDICATING METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS QUANTIFICATION OF SORAFENIB AND REGORAFENIB DRUG SUBTANCES BY USING RP-UPLC”. International Journal of Current Pharmaceutical Research, Vol. 12, no. 1, Jan. 2020, pp. 56-62, doi:10.22159/ijcpr.2020v12i1.36832.
Section
Original Article(s)