Author(s):
Gandhi Santosh Kumar, Badal Kumar Mandal
Email(s):
badalmandal@vit.ac.in , santoshkumar.gandhi@gmail.com
DOI:
10.52711/0974-360X.2024.00705 
Address:
Gandhi Santosh Kumar, Badal Kumar Mandal*
Department of Chemistry, School of Advance Sciences, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu – 632014, India.
*Corresponding Author
Published In:
Volume - 17,
Issue - 9,
Year - 2024
ABSTRACT:
In this study, an efficient, reproducible, and reliable stability indicating reverse-phase high-performance liquid chromatography (HPLC) method has been developed for the simultaneous quantification of Tegafur (TGFR), Gimeracil (GMRL), and Oteracil (ORCL) in bulk and dose formulation with a shorter run time (6min).TFGR, GMRL, and ORCL were separated using an isocratic method on a Waters C18 (250 mm x 4.6 mm × 5 µm) column with a mobile phase containing methanol and phosphate buffer (0.1M KH2PO4, pH 4.0) in a 50:50 (v/v) ratio. The detection wavelength was 275 nm and the flow rate was 1 mL/min. The new method demonstrated excellent linearity for TFGR (10 to 30µg/ml), GMRL (2.9 to 8.7µg/ml), and ORCL (7.9 to 23.70µg/ml). The method was found to be precise and accurate, with an RSD of 0.057% to 0.183% and a recovery rate of 98.66% to 100.52%. Stress degradation experiments have demonstrated that this method can be utilized to estimate TFGR, GMRL, and ORCL in the presence of their degradants. The method is suitable for determining TFGR, GMRL, and ORCL in bulk and capsule formulation (Tegonat).
Cite this article:
Gandhi Santosh Kumar, Badal Kumar Mandal. Development and Validation of a Stability-Indicating RP-HPLC Method for Simultaneous Estimation of Gimeracil, Oteracil, and Tegafur in Bulk and Dosage forms in the presence of Stress Degradation Impurities. Research Journal of Pharmacy and Technology. 2024; 17(9):4569-4. doi: 10.52711/0974-360X.2024.00705
Cite(Electronic):
Gandhi Santosh Kumar, Badal Kumar Mandal. Development and Validation of a Stability-Indicating RP-HPLC Method for Simultaneous Estimation of Gimeracil, Oteracil, and Tegafur in Bulk and Dosage forms in the presence of Stress Degradation Impurities. Research Journal of Pharmacy and Technology. 2024; 17(9):4569-4. doi: 10.52711/0974-360X.2024.00705 Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-9-66
REFERENCE:
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68(6): 394-424. https://doi.org/10.3322/caac.21492
2. Yadav AR, Mohite SK. Cancer- A Silent Killer: An Overview. Asian Journal Pharmaceutical Research. 2020; 10(3): 213-216. https://doi.org/10.5958/2231-5691.2020.00036.2
3. Saha D, Maity T, Jana M, Mandal S. Cancer Treatment Strategy-An Overview. Asian Journal of Pharmaceutical Technology. 2011; 1(2): 28-33.
4. Tiwari KJ, Jadhav K. Cancer is a Life-Threatening Disease: A Review. Research Journal of Pharmaceutical Dosage Forms and Technology. 2020; 12(2): 111-114. https://doi.org/10.5958/0975-4377.2020.00020.8
5. Kaur C, Kumar S, Singh S, Kaur H. Cancer: A Black Spot to Human Race!. Research Journal of Science and Technology. 2020; 12(1): 01-12. https://doi.org/10.5958/2349-2988.2020.00001.7
6. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Gastroenterology Review. 2019;14(1):26-38. https://doi.org/10.5114/pg.2018.80001
7. Shin WS, Xie F, Chen B, Yu P, Yu J, To KF, Kang W. Updated Epidemiology of Gastric Cancer in Asia: Decreased Incidence but Still a Big Challenge. Cancers (Basel). 2023; 15(9): 2639. https://doi.org/10.3390/cancers15092639
8. Kobayakawa M, Kojima Y. Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric cancer in adults when given in combination with cisplatin: a review comparing it with other fluoropyrimidine-based therapies. Onco Targets and Therapy. 2011; 4: 193-201. https://doi.org/10.2147/OTT.S19059
9. Liu H, Wang Y, Li G, Song W, Wang R. Clinical study of tegafur-gimeracil-oteracil potassium capsule (s-1) and oxaliplatin combination chemotherapy in advanced colorectal cancer. Journal of Cancer Research and Therapy. 2015; 11(2): 331-335. https://doi.org/10.4103/0973-1482.157339
10. Ishizuna K, Ninomiya J, Ogawa T, Kojima M, Tsuji E, Kawashima M, Nozaki M, Yamagishi H, Ueda Y. Effectiveness and safety of tegafur-gimeracil-oteracil potassium (TS-1) for metastatic breast cancer: a single-center retrospective study. Gan To Kagaku Ryoho. 2014; 41(13): 2577-2582.
11. Otsuka H, Fujii T, Toh U, Iwakuma N, Takahashi R, Mishima M, Takenaka M, Kakuma T, Tanaka M, Shirouzu K. Phase II clinical trial of metronomic chemotherapy with combined irinotecan and tegafur-gimeracil-oteracil potassium in metastatic and recurrent breast cancer. Breast Cancer. 2013; 22(4): 335-342. https://doi.org/10.1007/s12282-013-0483-1
12. Zhang X, Tian X, Wei Y, Deng H, Ma L, Chen Z. Activity and Safety of Tegafur, Gimeracil, and Oteracil Potassium for Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis. Journal of Oncology. 2021; 2021: 6690275. https://doi.org/10.1155/2021/6690275
13. Khar Kilam RK. Evolution of quality control in pharmaceutical technology. Journal of Advanced Pharmaceutical Technology & Research. 2013; 4(4): 172. https://doi.org/10.4103/2231-4040.121409
14. Haleem RM, Salem MY, Fatahallah FA, Abdelfattah LE. Quality in the pharmaceutical industry - A literature review. Saudi Pharm J. 2015; Oct; 23(5): 463-9. https://doi.org/10.1016/j.jsps.2013.11.004
15. Haritha KM, Khandapu BMK., Raju RR. Liquid chromatography dependent stability indicating methodology: development and authentication for formulations of capsule type containing tegafur, gimeracil, and oteracil. International Journal of Applied Pharmaceutics, 2023; 15(4): 71–81. https://doi.org/10.22159/ijap.2023v15i4.47831.
16. Vyas AJ, Jadav CD, Patel AI, Patel AB, Shah SR, Sheth D, Dholakia S. Review on Stability Indicating Assay Method or Forced Degradation Study: Strategy and Regulatory Consideration. Asian Journal of Pharmaceutical Analysis. 2023; 13(2): 131-9. https://doi.org/10.52711/2231-5675.2023.00022
17. Roge AB, Tarte PS, Kumare MM, Shendarkar GR, Vadvalkar SM. Forced Degradation Study: An Important Tool in Drug Development. Asian Journal of Pharmaceutical Research. 2013; 3(4): 198-201.
18. Shinde NG, Bangar BN, Deshmukh SM, Sulake SP, Sherekar DP. Pharmaceutical Forced Degradation Studies with Regulatory Consideration. Asian Journal of Research in Pharmaceutical Sciences. 2013; 3(4): 178-188.
19. Sutar SV, Yeligar VC, Patil SS. A Review: Stability Indicating Forced Degradation Studies. Research Journal of Pharmacy and Technology. 2019; 12(2): 885-890. https://doi.org/10.5958/0974360X.2019.00152.5.
20. International conference on the harmonization. ICH Stability testing of new drug substances and products Q1A (R2), 2003.
21. Hamid K. Analytical Method Development in Pharmaceutical Research: Steps involved in HPLC Method Development. Asian Journal of Pharmaceutical Research. 2017; 7(3): 203-207. https://doi.org/10.5958/2231-5691.2017.00031.4
22. Rajmane AD, Shinde KP. A Review of HPLC Method Development and Validation as per ICH Guidelines. Asian Journal of Pharmaceutical Analysis. 2023; 13(2): 143-1. https://doi.org/10.52711/2231-5675.2023.00024.
23. International conference on the harmonization. ICH harmonized tripartite guideline. Validation of analytical procedures: Text and methodology Q2(R1), 2005.