Author(s):
Prakashkumar B, Bhagyalakshmi C, Pulak Majumder, Koushik Nandan Dutta, Manoj Kumar Deka, Bhargab Jyoti Sahariah, Manish Majumder
Email(s):
prakashkumar_007@yahoo.co.in , bhagyachandran31@gmail.com , pulakmajumder@accp.co.in , koushik5dutta@gmail.com , manojpharmacy86@gmail.com , bhargabjyoti@gmail.com , manishphar33@gmail.com
DOI:
10.52711/0974-360X.2024.00500
Address:
Prakashkumar B1, Bhagyalakshmi C1, Pulak Majumder2, Koushik Nandan Dutta3, Manoj Kumar Deka4, Bhargab Jyoti Sahariah4, Manish Majumder5*
1Department of Pharmaceutical Analysis, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, BG Nagara - 571448, Karnataka, India.
2Department of Pharmacognosy, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, BG Nagara - 571448, Karnataka, India.
3Department of Pharmacognosy, NETES Institute of Pharmaceutical Sciences, Nemcare Group of Institution, Mirza, Kamrup, Assam 781125.
4Department of Pharmaceutics, NETES Institute of Pharmaceutical Sciences, Nemcare Group of Institution, Mirza, Kamrup, Assam 781125.
5Department of Pharmaceutical Chemistry, NETES Institute of Pharmaceutical Sciences, Nemcare Group of Institution, Mirza, kamrup, Assam 781125.
*Corresponding Author
Published In:
Volume - 17,
Issue - 7,
Year - 2024
ABSTRACT:
A precise and accurate liquid chromatography method was developed to simultaneously determine linagliptin and empagliflozin in spiked human plasma. The method utilized a C8 Eclipse Plus column (25cm X 5mm and 4.6µm) packed with L1 material, with a flow rate of 1mL/min. The mobile phase consisted of a mixture of acetonitrile, methanol, and 20mM potassium dihydrogen orthophosphate (pH 3.5) in a ratio of 26:19:55% (v/v). Detection was performed at 230nm, and the total run time was 15minutes. The retention time for linagliptin was 4.30 minutes, while for empagliflozin it was 10.35 minutes. The linear range for quantification was found to be 50-750 ng/mL for linagliptin and 30-960ng/mL for empagliflozin. The regression equations for linagliptin and empagliflozin were y = 181.24x+11241 and y = 393.64x+19552, respectively, with high regression coefficients (R2) of 0.9997 and 0.9995. Protein precipitation using a mixture of acetonitrile and methanol (70:30) was employed for extraction. The method demonstrated good recovery percentages ranging from 89.728±5.010 to 95.806±2.828 for linagliptin and 85.593±5.661 to 95.150±1.593 for empagliflozin. Extensive validation was conducted to assess linearity, accuracy, precision, recovery, and stability of the method.
Cite this article:
Prakashkumar B, Bhagyalakshmi C, Pulak Majumder, Koushik Nandan Dutta, Manoj Kumar Deka, Bhargab Jyoti Sahariah, Manish Majumder. A Simple Liquid Chromtographic Method for the Simultaneous Estimation of Antidiabetic Drugs in Spiked Human Plasma: Heteroscedasticity Study. Research Journal of Pharmacy and Technology. 2024; 17(7):3190-3. doi: 10.52711/0974-360X.2024.00500
Cite(Electronic):
Prakashkumar B, Bhagyalakshmi C, Pulak Majumder, Koushik Nandan Dutta, Manoj Kumar Deka, Bhargab Jyoti Sahariah, Manish Majumder. A Simple Liquid Chromtographic Method for the Simultaneous Estimation of Antidiabetic Drugs in Spiked Human Plasma: Heteroscedasticity Study. Research Journal of Pharmacy and Technology. 2024; 17(7):3190-3. doi: 10.52711/0974-360X.2024.00500 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2024-17-7-33
REFERENCES:
1. Virendra Singh Choudhary, Geeta Chaudhary. A Descriptive Study to Assess the Knowledge Regarding Diabetes Mellitus, Its Risk Factors and Complication among the Rural Community Sadiq, Faridkot (Punjab). Asian J. Nur. Edu. and Research. 2015; April-June; 5(2): 251-253.
2. Hazaratali Panari, Vegunarani.M. Study on Complications of Diabetes Mellitus among the Diabetic Patients. Asian J. Nur. Edu. and Research. 2016; 6(2): 171-182.
3. Sindhu L, Jaya Kumar B. Effectiveness of Educational Intervention on Body Mass Index (BMI) of Patients with Type 2 Diabetes Mellitus in South Indian Population. Asian J. Nursing Education and Research. 2018; 8(3): 434-436.
4. Parisa Parsa, Roya Ahmadinia-Tabesh, Younes Mohammadi. Assessment of the risk of Coronary Heart Disease in Diabetes Patients Type-II. Asian J. Nursing Education and Research. 2019; 9(2): 267-270.
5. Pushpendra Kumar, Titi Xavier Mangalathil, Vikas Choudhary. An experimental study to assess the effectiveness of structured teaching programme on knowledge regarding the management of diabetes mellitus among G.N.M. students in selected nursing school at Sikar, Rajasthan. Asian J. Management. 2014; 5(3): July-September: 329-331.
6. Himani Patel, Daxaben P. Patel. A Descriptive Study to Assess the Knowledge and Attitude regarding Self Administration of Insulin Injection among Diabetes Mellitus patient in selected Hospital of Visnagar City, in view of Information Booklet. Asian Journal of Nursing Education and Research. 2021; 11(4): 499-2.
7. Don Jose K, Femi Sebastian, Fiby Franklin, Divya Davis, Iriene B. Padanilath, Jeena Johnson. A study to assess the Knowledge regarding glycemic control and self- management among diabetic patients in Amala Institute of Medical Sciences, Thrissur. Asian Journal of Nursing Education and Research. 2021; 11(4): 571-6.
8. Gepsi Jain, Nahomi Clement. A Study to assess the knowledge regarding self management behaviour among Type II Diabetes Mellitus patients in prevention of COVID-19 at selected area, Alappuzha District, Kerala, India. Asian Journal of Nursing Education and Research. 2022; 12(4): 449-3.
9. Frampton JE. Empagliflozin: A Review in Type 2 Diabetes. Drugs [Internet]. 2018; 78(10): 1037–48. Available from: https://doi.org/10.1007/s40265-018-0937-z
10. Neumiller JJ. Empagliflozin: A new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Drugs Context. 2014; 2(June).
11. Neumiller JJ. Revisión de la farmacología, eficacia y seguridad de linagliptina en el tratamiento de pacientes con diabetes mellitus tipo 2. Ann Pharmacother. 2012; 46(3): 358–67.
12. Neumiller JJ, Setter SM. Review of Linagliptin for the Treatment of Type 2 Diabetes Mellitus. Clin Ther [Internet]. 2012; 34(5): 993–1005. Available from: http://dx.doi.org/10.1016/j.clinthera.2012.02.029
13. Ingelfinger JR, Rosen CJ. Clinical credence — SGLT2 inhibitors, diabetes, and chronic kidney disease. N Engl J Med. 2019; 380(24): 2371–3.
14. Elmasry MS, Hassan WS, Merey HA, Nour IM. Simple mathematical data processing method for the determination of sever overlapped spectra of linagliptin and empagliflozin in their pure forms and pharmaceutical formulation: Fourier self deconvulated method. Spectrochim Acta - Part A Mol Biomol Spectrosc [Internet]. 2021; 254: 119609. Available from: https://doi.org/10.1016/j.saa.2021.119609
15. Moussa BA, Mahrouse MA, Fawzy MG. Smart spectrophotometric methods for the simultaneous determination of newly co-formulated hypoglycemic drugs in binary mixtures. Spectrochim Acta - Part A Mol Biomol Spectrosc [Internet]. 2021; 257: 119763. Available from: https://doi.org/10.1016/j.saa.2021.119763
16. Suresh PS, Srinivas NR, Mullangi R. A concise review of the bioanalytical methods for the quantitation of sitagliptin, an important dipeptidyl peptidase-4 (DPP4) inhibitor, utilized for the characterization of the drug. Biomed Chromatogr. 2016; 30(5): 749–71.
17. Abbas Moussa B, Mahrouse MA, Fawzy MG. A validated LC-MS/MS method for simultaneous determination of linagliptin and metformin in spiked human plasma coupled with solid phase extraction: Application to a pharmacokinetic study in healthy volunteers. J Pharm Biomed Anal [Internet]. 2019; 163: 153–61. Available from: https://doi.org/10.1016/j.jpba.2018.09.052
18. Kobuchi S, Ito Y, Yano K, Sakaeda T. A quantitative LC-MS/MS method for determining ipragliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, and its application to a pharmacokinetic study in rats. J Chromatogr B Anal Technol Biomed Life Sci [Internet]. 2015; 1000: 22–8. Available from: http://dx.doi.org/10.1016/j.jchromb.2015.07.013
19. Li X, Liu L, Deng Y, Li Y, Zhang P, Wang Y, et al. Pharmacokinetics and bioequivalence of a generic empagliflozin tablet versus a brand-named product and the food effects in healthy Chinese subjects. Drug Dev Ind Pharm [Internet]. 2020; 46(9): 1487–94. Available from: http://dx.doi.org/10.1080/03639045.2020.1810263
20. Jadhav SB, Reddy PS, Narayanan KL, Bhosale PN. Development of RP-HPLC, stability indicating method for degradation products of linagliptin in presence of metformin HCl by applying 2 level factorial design; and identification of impurity-VII, VIII and IX and synthesis of impurity-VII. Sci Pharm. 2017; 85(3): 1–17.
21. Shah PA, Shrivastav PS, Sharma V, Yadav MS. Challenges in simultaneous extraction and chromatographic separation of metformin and three SGLT-2 inhibitors in human plasma using LC–MS/MS. J Pharm Biomed Anal [Internet]. 2019; 175: 112790. Available from: https://doi.org/10.1016/j.jpba.2019.112790
22. Dietrich N, Kolibabka M, Busch S, Bugert P, Kaiser U, Lin J, et al. The dpp4 inhibitor linagliptin protects from experimental diabetic retinopathy. PLoS One. 2016; 11(12): 1–17.
23. van der Aart-van der Beek AB, Wessels AMA, Heerspink HJL, Touw DJ. Simple, fast and robust LC-MS/MS method for the simultaneous quantification of canagliflozin, dapagliflozin and empagliflozin in human plasma and urine. J Chromatogr B Anal Technol Biomed Life Sci [Internet]. 2020; 1152: 122257. Available from: https://doi.org/10.1016/j.jchromb.2020.122257
24. Zhang H, Uthman L, Bakker D, Sari S, Chen S, Hollmann MW, et al. Empagliflozin Decreases Lactate Generation in an NHE-1 Dependent Fashion and Increases α-Ketoglutarate Synthesis From Palmitate in Type II Diabetic Mouse Hearts. Front Cardiovasc Med. 2020; 7(December): 1–10.
25. Mourad SS, El-Kimary EI, Barary MA, Hamdy DA. Pharmacokinetic interaction between linagliptin and tadalafil in healthy Egyptian males using a novel LC-MS method. Bioanalysis. 2019; 11(14): 1321–36.
26. Suda M, Shimizu I, Yoshida Y, Hayashi Y, Ikegami R, Katsuumi G, et al. Inhibition of dipeptidyl peptidase-4 ameliorates cardiac ischemia and systolic dysfunction by up-regulating the FGF-2/EGR-1 pathway. PLoS One. 2017; 12(8): 1–18.
27. Kobuchi S, Yano K, Ito Y, Sakaeda T. A validated LC-MS/MS method for the determination of canagliflozin, a sodium–glucose co-transporter 2 (SGLT-2) inhibitor, in a lower volume of rat plasma: application to pharmacokinetic studies in rats. Biomed Chromatogr. 2016; 30(10): 1549–55.
28. Kobuchi S, Matsuno M, Fukuda E, Ito Y, Sakaeda T. Development and validation of an LC-MS/MS method for the determination of tofogliflozin in plasma and its application to a pharmacokinetic study in rats. J Chromatogr B Anal Technol Biomed Life Sci [Internet]. 2016; 1027: 227–33. Available from: http://dx.doi.org/10.1016/j.jchromb.2016.05.053
29. Airapetian V, Glocer A, Gronoff G. The early Earth under a superflare and super-CME attack: Prospects for life. Proc Int Astron Union. 2015; 11(S320): 409–15.
30. Bhole RP, Wankhede SB, pandey M. Stability Indicating HPTLC Method for Simultaneous Estimation of Empagliflozin and Linagliptin in Pharmaceutical Formulation. Anal Chem Lett. 2017; 7(1): 76–85.
31. Ayoub BM. UPLC simultaneous determination of empagliflozin, linagliptin and metformin. RSC Adv. 2015; 5(116): 95703–9.
32. Donepudi S, Achanta S. Validated HPLC-UV method for simultaneous estimation of linagliptin and empagliflozin in human plasma. Int J Appl Pharm. 2018; 10(3): 56–61.
33. Marie AA, Salim MM, Kamal AH, Hammad SF, Elkhoudary MM. Analytical quality by design based on design space in reversed-phase-high performance liquid chromatography analysis for simultaneous estimation of metformin, linagliptin and empagliflozin. R Soc Open Sci. 2022; 9(6).
34. Patel IM, Chhalotiya UK, Jani HD, Kansara D, Kachhiya HM, Shah DA. Simultaneous quantification of empagliflozin, linagliptin and metformin hydrochloride in bulk and synthetic mixture by RP–LC method. Futur J Pharm Sci [Internet]. 2021; 7(1): 1–10. Available from: https://doi.org/10.1186/s43094-021-00332-1
35. Patel IM, Chhalotiya UK, Jani HD, Kansara D, Shah DA. Densitometric simultaneous estimation of combination of empagliflozin, linagliptin and metformin hydrochloride used in the treatment of type 2 diabetes mellitus. J Planar Chromatogr - Mod TLC. 2020; 33(2): 109–18.
36. Vankalapati KR, Alegete P, Boodida S. Stability-indicating ultra performance liquid chromatography method development and validation for simultaneous estimation of metformin, linagliptin, and empagliflozin in bulk and pharmaceutical dosage form. Biomed Chromatogr. 2021; 35(4): 5–15.
37. FDA F and DA. Bioanalytical Method Validation Guidance. Food Drug Adm. 2018; 1043(May): 25.
38. Analytical Method Development and Method Validation for the Simultaneous Estimation of Metformin hydrochloride and Pioglitazone hydrochloride in Tablet Dosage Form by RP-HPLC. Asian J. Pharm. Ana. 2012; 2(3): July-Sept. 85-89.
39. Swapnil J. Dengle, Shriram M. Pathak, Chandra Mohan, Arumugam Karthik, Prashant Musmade, Krishnamurthy Bhat, Nayanabhirama Udupa. Analysis of Midazolam in Small Volumes of Plasma Using High Performance Liquid Chromatography and UV-Detection Method: Pharmacokinetics of Midazolam in Rats. Asian J. Research Chem. 2011; 4(3): March 406-414.
40. Niraj Vyas, Sangita Panchal. Development and Validation of RP-HPLC Method for Simultaneous Estimation of Nebivolol and Indapamide in Pharmaceutical Dosage Form. Asian J. Pharm. Ana. 2014; 4(3): July-Sept. 98-102.
41. Almeida AM, Castel-Branco MM, Falcão AC. Linear regression for calibration lines revisited: Weighting schemes for bioanalytical methods. J Chromatogr B Anal Technol Biomed Life Sci. 2002; 774(2): 215–22.
42. Sonawane SS, Chhajed SS, Attar SS, Kshirsagar SJ. An approach to select linear regression model in bioanalytical method validation. J Anal Sci Technol. 2019; 10(1): 1–7.
43. Mercolini L, Mandrioli R, Finizio G, Boncompagni G, Raggi MA. Simultaneous HPLC determination of 14 tricyclic antidepressants and metabolites in human plasma. J Sep Sci. 2010; 33(1): 23–30.
44. Donepudi S, Achanta S. Simultaneous estimation of saxagliptin and dapagliflozin in human plasma by validated high performance liquid chromatography - Ultraviolet method. Turkish J Pharm Sci. 2019; 16(2): 227–33.