Author(s):
Prajakta Kapadnis, Priyanka Gawarkar-Patil, Shital Godse, Bhavna S. Mahajan
Email(s):
bhavnamahajan15@gmail.com
DOI:
10.52711/0974-360X.2025.00644 
Address:
Prajakta Kapadnis2, Priyanka Gawarkar-Patil3, Shital Godse2, Bhavna S. Mahajan1,2*
1Sinhgad Institute of Pharmacy, Narhe, Pune - 411041, Affiliated to Savitribai Phule Pune University, Ganeshkhind, Pune - 411007, Maharashtra, India.
2Vishwakarma University School of Pharmacy, Pune - 411048, Maharashtra, India.
3BVDU Poona College of Pharmacy, Pune - 411038, Maharashtra, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 9,
Year - 2025
ABSTRACT:
This study aimed to demonstrate methodologies for employing liquid chromatography and liquid chromatography-mass spectrometry to identify, elute, and elucidate the structures of Remogliflozin (RMG) degradation products without isolating them from reaction mixtures. A review of existing literature reveals the absence of a specific tandem mass spectrometric technique for characterizing Remogliflozin’s degradation products. According to the International Conference on Harmonization guideline, oxidative, thermal, photolytic, and acid-base hydrolysis stress tests were conducted on Remogliflozin etabonate. Two major degradation products were identified: one under acidic conditions and another under basic conditions. A C18 column was utilized to separate each degradation product using high-performance liquid chromatography in isocratic mode. The method was validated with a correlation coefficient of 0.9998 and other validation parameters by the guidelines specified by the International Conference on Harmonization. The tandem mass spectrometric analysis of the degradation products facilitated the establishment of their chemical structures. Virtual toxicity analysis suggested that one of the degradation products could be hepatotoxic.
Cite this article:
Prajakta Kapadnis, Priyanka Gawarkar-Patil, Shital Godse, Bhavna S. Mahajan. HPLC and LC-MS/MS Investigations for Remogliflozin Etabonate Degradation Product Identification and Characterization. Research Journal of Pharmacy and Technology. 2025;18(9):4491-6. doi: 10.52711/0974-360X.2025.00644
Cite(Electronic):
Prajakta Kapadnis, Priyanka Gawarkar-Patil, Shital Godse, Bhavna S. Mahajan. HPLC and LC-MS/MS Investigations for Remogliflozin Etabonate Degradation Product Identification and Characterization. Research Journal of Pharmacy and Technology. 2025;18(9):4491-6. doi: 10.52711/0974-360X.2025.00644 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-9-64
7. REFERENCES:
1. Fujimori Y, Katsuno K, Nakashima I, Ishikawa-Takemura Y, Fujikura H, Isaji M. Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. Journal of Pharmacology and Experimental Therapeutics. 2008; 327: 268–76.
2. Kapur A, O'Connor-Semmes R, Hussey EK, Dobbins RL, Wenli T, Marcus H, et al. First human dose-escalation study with remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type II diabetes mellitus. BMC Pharmacology and Toxicology. 2013; 13: 14-26.
3. Nasser M. Remogliflozin etabonate: a novel SGLT2 inhibitor for treatment of diabetes mellitus. Expert Opinion on Investigational Drugs. 2015; 24: 1381-7.
4. Shinde S, Bardiya R, Jain P, Shikhedkar A, Nagar D. Comparison of acid degradant product with metabolic pathway of remogliflozin etabonate in developed and validated RP-HPTLC method. Indian Drugs. 2022; 59(11): 46-53. doi:10.53879/id.59.11.13183.
5. Sai PN, Venkateswarlu BS, Kumudhavalli MV, Muruganantham V. Novel stability indicating LC-MS/MS method for the simultaneous estimation of Remogliflozin etabonate and vildagliptin in human plasma. Journal of Medical Pharmaceutical and Allied Sciences. 2021; 5: 3718-25.
6. Itigimatha N, Chadchan KS, Yallur BC, Hadagali MD. Simple and sensitive RP-HPLC and UV spectroscopic methods for the determination of Remogliflozin etabonate in pure and pharmaceutical formulations. Turkish Journal of Pharmaceutical Sciences. 2022; 19: 213-9. doi:10.4274/tjps.galenos.2021.55381. PMID: 35510349; PMCID: PMC9083516.
7. Bhatkar T, Amol V, Badkhal N, Bhajipale S. Stability indicating RP-HPLC method development and validation for the estimation of Remogliflozin etabonate in bulk and pharmaceutical dosage form. International Journal of Pharmaceutical Research. 2023; 15: 3452-61.
8. Trivedi SV. Stability indicating RP-HPLC method development and validation for simultaneous estimation of remogliflozin etabonate and metformin HCl in synthetic mixture and tablet dosage form. World Journal of Pharmaceutical Research. 2021; 10: 981-93.
9. Attimarad M, Venugopala KN, Nair AB, Sreeharsha N, Deb PK. Experimental design approach for quantitative expressions of simultaneous quantification of two binary formulations containing Remogliflozin and Gliptins by RP-HPLC. Separations. 2022; 9. doi:10.3390/separations9020023.
10. Tayade AB, Patil AS, Shirkhedkar AA. Development and validation of zero-order UV-spectrophotometric method by area under curve technique and high-performance thin layer chromatography for the estimation of remogliflozin etabonate in bulk and in-house tablets. Rapid Pharmaceutical Analysis and Quality Assurance. 2019; 3: 1-5.
11. Shah D, Gondalia I, Patel V, Mahajan A, Chhalotiya UK. Stability indicating liquid chromatographic method for the estimation of remogliflozin etabonate. Journal of Chemical Metrology. 2020; 14: 125-32.
12. Tammisetty MR, Challa BR, Puttagunta SB. A novel analytical method for the simultaneous estimation of Remogliflozin and Metformin Hydrochloride by UPLC/PDA in bulk and formulation application to the estimation of product traces. Turkish Journal of Pharmaceutical Sciences. 2021; 18: 296-305.
13. ICH Q1A(R2) Guideline: Stability testing of new drug substances and products. International Conference on Harmonisation (ICH), IFMPA, Geneva, Switzerland. 2003.
14. Bhavya B, Nagaraju P, Mounika V, Indira P. Stability Indicating RP-HPLC Method Development and Validation for Simultaneous Estimation of Albendazole and Ivermectin in Pharmaceutical Dosage form. Asian Journal of Pharmaceutical Analysis. 2017; 7(1): 6-14. doi: 10.5958/2231-5675.2017.00002.3
15. Patil SD, Amurutkar SV, Upasani CD. Development and Validation of Stability Indicating RP-HPLC Method for Empagliflozin. Asian Journal of Pharmaceutical Analysis. 2016; 6(4): 201-206. doi: 10.5958/2231-5675.2016.00030.2
16. Bhamare P, Dubey R, Upmanyu N, Umadoss P. A simple HPLC Method for In-Vitro Dissolution study of Brivaracetam in Pharmaceutical Dosage Form. Asian Journal of Pharmaceutical Analysis. 2021; 11(1): 1-8. doi: 10.5958/2231-5675.2021.00001.6
17. Rucha AP, Meghna PP, Hasumati AR, Nehal S. Forced Degradation Studies of Olmesartan Medoxomil and Characterization of Its Major Degradation Products by LC-MS/MS, NMR, IR and TLC. Asian Journal of Pharmaceutical Analysis. 2015; 5(3): 119-125.
18. Hamid K, Javed A. Identification of Impurities and Degradation Products in Pharmaceutical Products- Role of Hyphenated Techniques. Asian Journal of Pharmaceutical Analysis. 2017; 7(1): 31-35.
19. Vashi D, Chaudhari H. Development and Validation of UV Spectroscopic Method for Simultaneous Estimation of Remogliflozin Etabonate and Vildagliptin in bulk and Pharmaceutical Dosage Form. Asian Journal of Pharmaceutical Analysis. 2023; 13(2): 69-3.
20. Hamid K. Identification and Characterization of Degradation Products of Valsartan by UPLC/Q-TOF-MS Technique. Asian Journal of Pharmaceutical Research. 2021; 11(1): 1-5.
21. Hamid K, Mushir A, Alka A, Javed A. Application of Validated UPLC/Q-TOF-MS Method for Simultaneous Determination of Telmisartan, Hydrochlorothiazide and their Degradation Products in Tablets. Asian Journal of Research in Pharmaceutical Sciences. 2017; 7(2): 105-111.
22. Effat S, Nazanin SR, Farhad A, Arsalan N, Maliheh B, et al. Validated Stability-Indicating HPLC Method for the Determination of Pantoprazole in the Presence of Its Degradation Products. Asian Journal of Research in Chemistry. 2010; 3(4): 879-884.
23. Basima Arous, Mhd Amer Al-Mardini. LC-MS method to Estimate the Relation between Drug Stability Study and Impurity Profile of Dabigatran etexilate. Research Journal of Pharmacy and Technology. 2018; 11(3): 1119-1130.
24. ICH Q2(R1) Guideline: Validation of Analytical Procedures: Text and Methodology. International Conference on Harmonization (ICH), IFPMA, Geneva, Switzerland. 2005.
25. Mahajan BS, Kawale LA, Nade VS, Unawane SA, Sajimon L, Kapadnis P. Design, synthesis, and evaluation of anxiolytic activity of 2-(4-phenylpiperazin-1-yl)-1H-benz[d]imidazole and 2-(4-phenylpiperazin-1-methyl)-1H-benz[d]imidazole derivatives. Future Journal of Pharmaceutical Sciences. 2024; 10. doi:10.1186/s43094-024-00626-0.
26. Mahajan BS, Miniyar PB. Identification, separation, and characterization of degradation products of triamcinolone hexacetonide using LC and LC-MS/MS. International Journal of Applied Pharmaceutics [Internet]. 2024; 16(3). Available from: https://journals.innovareacademics.in/index.php/ijap/article/view/50122.
27. Mahajan BS, Miniyar PB, Chodankar R, Mahajan AA. Liquid chromatography and liquid chromatography coupled with tandem mass spectrometry studies for the identification and characterization of degradation products of lobeglitazone. Separation Science Plus [Internet]. 2024. doi:10.1002/sscp.202300223.