Chromatographic study of sitagliptin and ertugliflozin under quality-by-design paradigm
DOI:
https://doi.org/10.1590/s2175-97902023e21328%20%20%20Keywords:
AQbD, HPLC, Sitagliptin, Ertugliflozin, Stability-indicatingAbstract
The present study entails the systematic development and validation of a stability-indicating RP-HPLC method for the analysis of sitagliptin and ertugliflozin in a fixed-dose combination. Analytical quality by design (AQbD) concepts were used to define critical method variables, employing Pareto risk assessment and a Placket-Burman screening design, preceded by a Box-Behnken design with response surface analysis to optimise critical method parameters such as % acetonitrile (X1), buffer pH (X2) and column oven temperature (X3). Multiple response optimisation (Derringer’s desirability) of variables was accomplished by studying critical analytical attributes, such as resolution, retention time and theoretical plates. The title analytes were separated effectively on a PRONTOSIL C18 column at 37 °C using a mobile phase of acetonitrile:acetate buffer, pH 4.4 (36:64 percent v/v), pumped at a flow rate of 1 mL/min, and UV detection at 225 nm. Linearity was observed over a concentration range of 25-150 µg/mL and 3.75-22.5 µg/mL at retention times of 2.82 and 3.92 min for sitagliptin and ertugliflozin, respectively. The method obeyed all validation parameters of the ICH Q2(R1) guidelines. The proposed robust method allows the study of the selected drugs in pharmaceutical dosage forms as well as in drug stability studies under various stress conditions.
Downloads
References
Amtul HH, Yunoos M. A new validated stability indicating RP-HPLC method for the simultaneous estimation of sitagliptin and ertugliflozin in bulk and tablet dosage form. Indo Am J Pharm Sci. 2018;5(09):8785-8794.
Anjali M, Shreshta M, Prasanna R, Shrisha T, Sathish KM. Method development and validation of ertugliflozin and sitagliptin by using simultaneous equation method. J Innov Pharm. 2019;3(1):22-28.
Anjaneyulu RB. A validated RP-HPLC charged aerosol detector technique for the simultaneous estimation of sitagliptin and ertugliflozin in pure and pharmaceutical dosage forms. Asian J Pharm Clin Res. 2019;12(5):236-240.
Aruna G, Prasad KVSRG, Bharathi K. Application of quality by design approach in RP-HPLC method development for simultaneous estimation of saxagliptin and dapagliflozin in tablet dosage form. Braz J Pharm Sci. 2019;55:2-10.
Awotwe-Otoo D, Agarabi C, Faustino PJ, Habib MJ, Lee S, Khan MA, et al. Application of quality by design elements for the development and optimization of an analytical method for protamine sulfate. J Pharm Biomed Anal. 2012;62:61-67.
Barnard K, Cox ME, Green JB. Clinical utility of fixed combinations of sitagliptin-metformin in treatment of type 2 diabetes. Diabetes Metab Syndr Obes. 2010;3:363-372.
Candioti LV, De Zan MM, Cámara MS, Goichoechea HC. Experimental design and multiple response optimization. Using the desirability function in analytical methods development. Talanta. 2014;124:123-138.
China BD. Novel stress indicating RP-HPLC method development and validation for the simultaneous estimation of ertugliflozin and sitagliptin in bulk and its formulation. Orient J Chem. 2018;34(5):2554-2561.
Costa NR, Lourenço J, Pereira ZL. Desirability function approach: a review and performance evaluation in adverse conditions. Chemom Intell Lab Syst. 2011;107(2):234-44.
Deidda R, Orlandini S, Hubert P, Hubert C. Risk-based approach for method development in pharmaceutical quality control context: a critical review. J Pharm Biomed Anal. 2018;161:110-121.
Giordani CFA, Campanharo S, Wingert NR, Bueno LM, Manoel JW, Garcia CV. Determination of sitagliptin in the presence of its organic impurities using Box-Behnken experimental design for robustness assessment. Pharmazie. 2018;73(5):442-446.
Ferey L, Raimbault A, Rivals I, Gaudin K. UHPLC method for multiproduct pharmaceutical analysis by quality-by-design. J Pharm Biomed Anal. 2018;148:361-368.
Ganorkar SB, Dhumal DM, Shirkhedkar AA. Development and validation of simple RP-HPLC-PDA analytical protocol for zileuton assisted with design of experiments for robustness determination. Arabian J Chem. 2017;10(2):273-282.
Gurrala S, Shivaraj, Subrahmanyam CVS, Anumolu PD, Saraf G. Analytical quality by design assisted HPLC method for quantification of canagliflozin/metformin and stability studies. Indian J Pharm Educ Res. 2019;53(4):699-709.
Harshalatha P. A novel RP-HPLC method for simultaneous determination of ertugliflozin and sitagliptin in bulk and tablet dosage form. Int J Res Pharm Sci. 2018;9(3):1042-1050.
Hemant B, Moolchand K, Saranjit S, Sarwar B, Bhupinder S. Quality by design (QbD) in analytical sciences: an overview. Pharm Times. 2014;46(8):71-75.
Hubert C, Houari S, Rozet E, Lebrun P, Hubert P. Towards a full integration of optimization and validation phases: an analytical-quality-by-design approach. J Chromatogr A. 2015;1395:88-98.
International Conference of Harmonization. ICH. Q2(R1), Validation of analytical procedures: text and methodology. Geneva: International Conference on Harmonization; 1994.
International Conference of Harmonization. ICH. Q1A(R2), Stability testing of new drug substances and products. Geneva: International Conference on Harmonization; 2003.
Jain A, Beg S, Saini S, Sharma T, Katare OP, Singh B. Application of chemometric approach for QbD-enabled development and validation of an RP-HPLC method for estimation of methotrexate. J Liq Chromatogr Relat Technol. 2019;42(15-16):502-512.
Jiu XF, Shang D, Chen Y, Wang Y, Huang L, Peng D, et al. A high-performance liquid chromatography method for quantitative determination assay of sitagliptin in rat plasma and its application in pharmacokinetic study. J Chin Pharm Sci. 2011;20(1):63-69.
Karimulla SK, Vasanth PM, Ramesh T, Ramesh M. Method development and validation of sitagliptin and metformin using reverse phase HPLC method in bulk and tablet dosage form. Pharm Lett. 2013;5(5):168-174
Kumari KS, Bandhakavi S. Development and validation of stability-indicating RP-HPLC method for the simultaneous determination of ertugliflozin pidolate and metformin hydrochloride in bulk and tablets. Future J Pharm Sci. 2020;6:66-68.
Lange ADC, Gasperin FT, Passos CS, Todeschini V, Volpato NM, Schapoval EES. Stability-indicating LC assay with determination of system suitability limits by a robustness test for sitagliptin in tablets and assessment of cytotoxicity for degradation products. Curr Pharm Anal. 2012a;8(4):360-369.
Lange ADC, Gasperin FT, Barth AB, Todeschini V, Volpato NM, Schapoval EES. Application of factorial design and study of photodegradation kinetics for the determination of sitagliptin by capillary electrophoresis. Curr Anal Chem. 2012b;8(4):116-123.
Lin Q, Kahsay G, Waal TD, Zhu P, Tam M, Teughels R, et al. Improved liquid chromatographic method for quality control of spiramycin using superficially porous particles. J Pharm Biomed Anal. 2018;149:57-65.
Markham A. Ertugliflozin: First Global Approval. Drugs. 2018;78(4):513-519.
Musters J, Bos VDL, Kellenbach E. Applying QbD principles to develop a generic UHPLC method which facilitates continual improvement and innovation throughout the product lifecycle for a commercial API. Org Process Res Dev. 2013;17(1):87-96.
Patel M, Kothari C. Comprehensive stability-indicating method development of avanafil phosphodiesterase type 5 inhibitor using advanced quality-by-design approach. J Anal Sci Tech. 2020;11:1-14.
Politis SN, Colombo P, Colombo G, Rekkas DM. Design of experiments (DoE) in pharmaceutical development. Drug Develop Ind Pharm. 2017;43(6):889-901.
Pradipbhai DK, Deepak N, Srinivas R, Gananadhamu S. Application of experimental design and response surface technique for selecting the optimum RP-HPLC conditions for the determination of moxifloxacin HCl and ketorolac tromethamine in eye drops. J Saudi Chem Soc. 2017;21(1):373-82.
Ramalingam P, Bhadraya K, Reddy YP. Analytical quality by design: a tool for regulatory flexibility and robust analytics. Int J Anal Chem. 2015;1-9.
Reddy BV, Raman N, Kumar BS, Rambabu C. Chiral separation of sitagliptin phosphate enantiomer by HPLC using amylose based chiral stationary phase. J Pharm Res. 2013;7(6):546-550.
Reid GL, Cheng G, Fortin DT, Harwood JW, Morgado JE, Wang J, et al. Reversed-phase liquid chromatographic method development in an analytical quality by design framework. J Liq Chromatogr Relat Technol. 2013;36(18):2612-2638.
Sahu PK, Ramisetti NR, Cecchi T, Swain S, Patro CS, Panda J. An overview of experimental designs in HPLC method development and validation. J Pharm Biomed Anal. 2018;147:590-611.
Sangshetti JN, Deshpande M, Zaheer Z, Shinde DB, Arote R. Quality by design approach: regulatory need. Arabian J Chem. 2017;10(2):S3412-S3425.
Steglujan Ò. Ertugliflozin and sitagliptin tablets for oral use initial US approval. Kenilworth New Jersey: Merck and Co Inc. 2017;23.
Suneetha A, Mounika V, Shaik MS. Development and validation of stability indicating RP-HPLC method for the simultaneous estimation of sitagliptin and ertugliflozin in bulk and tablet dosage forms. Asian J Pharm Anal. 2020;10(2):81-85.
Suryawanshi D, Durgesh KJ, Umesh S, Purnima DA. Development and validation of a stability-indicating RP-HPLC method of cholecalciferol in bulk and pharmaceutical formulations: analytical quality by design approach. J Appl Pharm Sci. 2019:9(6):21-32.
Venkateswara RP, Lakshmana RA, Prasad SVUM. Development and validation of a method for simultaneous estimation of sitagliptin and ertugliflozin in rat plasma by LC-MS method. Curr Pharm Anal. 2021;17(8):1060-1074.
Vogt FG, Kord AS. Development of quality-by-design analytical methods. J Pharm Sci. 2011;100(3):797-812.
Zhang X, Hu C. Application of quality by design concept to develop a dual gradient elution stability-indicating method for cloxacillin forced degradation studies using combined mixture process variable models. J Chromatogr A. 2017;1514:44-53.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on line journal has open and free access.
