Author(s):
M. C. Damle, D. S. Rathod, A. D. Sujgure
Email(s):
damle_mc@aissmscop.com
DOI:
10.52711/2231-5675.2025.00003 
Address:
M. C. Damle1*, D. S. Rathod2, A. D. Sujgure3
1Head of Department, Pharmaceutical Quality Assurance, AISSMS College of Pharmacy, Pune, Maharashtra.
2,3Master of Pharmacy, Department of Pharmaceutical Quality Assurance, AISSMS College of Pharmacy, Pune, Maharashtra.
*Corresponding Author
Published In:
Volume - 15,
Issue - 1,
Year - 2025
ABSTRACT:
A simple, newand rapid stability indicating HPTLC method has been developed and validated for estimation of Trimetazidine Dihydrochloride and Metoprolol Tartrate in combination. These drugs are available as tablets for the treatment of ischemia. Chromatographic separation of the drugs was performed on aluminum plates pre-coated with silica gel 60 F254 as the stationary phase and the solvent system consisted of n-butanol: methanol: ammonia (10:4:2 v/v/v). Densitometric evaluation of the separated zones was performed at 225 nm. The two drugs were satisfactorily resolved with Rf values 0.26, and 0.70 for Trimetazidine Dihydrochloride and Metoprolol Tartrate, respectively. The linearity was observed in the range of 700-3500 ng/band for Trimetazidine Dihydrochloride and 1000-5000 ng/band for Metoprolol Tartrate. Both drugs were exposed to stress degradation conditions like hydrolysis at different pH, oxidation, photolytic and thermal degradation. The developed method was validated according to ICH guidelines. The method can be used for the routine quantitative determination of Trimetazidine dihydrochloride and Metoprolol tartrate in combination.
Cite this article:
M. C. Damle, D. S. Rathod, A. D. Sujgure. A New Stability Indicating HPTLC Method Development and Validation for Estimation of Trimetazidine Dihydrochloride and Metoprolol Tartrate. Asian Journal of Pharmaceutical Analysis. 2025;15(1):13-9. doi: 10.52711/2231-5675.2025.00003
Cite(Electronic):
M. C. Damle, D. S. Rathod, A. D. Sujgure. A New Stability Indicating HPTLC Method Development and Validation for Estimation of Trimetazidine Dihydrochloride and Metoprolol Tartrate. Asian Journal of Pharmaceutical Analysis. 2025;15(1):13-9. doi: 10.52711/2231-5675.2025.00003 Available on: https://ajpaonline.com/AbstractView.aspx?PID=2025-15-1-3
REFERENCES:
1. Parfit and Martindale. The Complete Drug Reference: Edn 3, Vol-I, Pharmaceutical Press, 2007, pp.1035-1036.
2. Harpey C, Clauser P, Labrid C, Freyria JL, Poirier JP. Cardiovas Drug Rev. 1989: pp.92-312.
3. Ciapponi A, Pizarro R, Harrison J. Cochrane Database Syst. Rev; 2005; 19: pp.1-54.
4. Hinge MA, Mahida RJ, Sojitra P. Development and validation of a spectrophotometric method for simultaneous estimation of trimetazidine hydrochloride and metoprolol succinate in the pharmaceutical dosage form. Int. J. Pharm.Sci.Rev. 2015; 31(1): 217-222.
5. Naga PY, Archana S, Poornima Y, Lalitha S, Lalitha M. Development and validation of a spectrometric method for determination of trimetazidine in the pharmaceutical dosage form. Prasanna et al Int J Pharm Sci Res. 2013; 4(3): 1131-1134.
6. Ravi M, Veeraiah T, Venkata CH, Reddy R. Spectrophotometric determination of trimetazidine using acidic triphenylmethane dyes. Int JRes Pharm Chemi. 2018; 8(3):412–21.
7. Mani G, Pushparaj H, Athanari SK, Peng MM, Hyun TJ. Spectroscopic method for determination of Trimetazidine in formulation using Chloranil as chromogenic agent. Eurasian J Analytical Chem. 2011; 6(2); 22-30.
8. Hemant K. Jain, Deepak D. Deore. Development and Validation of Spectrophotometric Method for Determination of Trimetazidine Hydrochloride in Bulk and Tablet Dosage Form. Research J. Pharm. and Tech 2016; 9(9):1457-1460. doi: 10.5958/0974-360X.2016.00282.1
9. Walaa E, Omnia A, Ismaiel, Magda Y. El-Mammli, Abdalla S. Determination of atenolol and trimetazidine in pharmaceutical tablets and human urine using a highperformance liquid Chromatography-Photo Diode Array Detection Method. Int J Analytical Chem. 2019:1687-8779
10. Farzana H, Sharja N, Hasib AH, Tajdika J.Validation of high performance liquid chromatography (HPLC) method for determination of trimetazidine in pharmaceutical dosage form.ejbps.2017; 4(7):66-73.
11. Mirjana BM, Darko PI, Igor BP,Andjelija MM, Biljana SJ. Computer-assisted optimization and validation of LC analysis of trimetazidine dihydrocloride and its impurities. J Chrom Sci. 2008; 46.
12. Nagula S, Thota S, Venishetty RK. Development and validation of a stability indicating RP-HPLC method for the determination of trimetazidine dihydrocloride. Der Pharma Chemica. 2014; 6(1): 149-154.
13. Simmy OT, Rita MC, Amin PD. Stability indicating HPTLC determination of trimetazidine as bulk drug and in pharmaceutical formulations. J Pharm Biomedical Analysis. 2001; 25:15-20.
14. Soliman SM. Factor optimization study to develop and validate a reversed-phase thin-layer chromatography method for the determination of trimetazidine dihydrochloride and its reported impurities in pharmaceuticals. J Planar Chrom-Mod TLC. 2019; 32(4): 273–83.
15. Tarek SB, Tamer, Clark CR. Stability-indicating determination of trimetazidine dihydrocloride in presence of two of its related substances using a direct GC/MS method. J AOAC Int. 2014; 97(6): 1514-1518.
16. European Pharmacopoeia 5.0, 01/2005; 2028, monograph of Metoprolol Tartrate. 2033-2034.
17. Indian Pharmacopoeia. Published by the Government of India, Ministry of Health and Family Welfare, the Indian Pharmacopoeia Commission, Ghaziabad. 2018; 3: 2587-2588.
18. Beckett AH and Stenlake JB. Practical Pharmaceutical Chemistry, CBS Publishers and Distributors, New Delhi, India, Vol I and II, 2000.
19. Patel A, Patel D, Patel D, Sheth A, Shah UJ. Method development and validation for simultaneous estimation of benidipine dydrochloride and metoprolol succinate in tablet. Journal of Drug Delivery and Therapeutics. 2019; 9(6): 28-33.
20. Sanapati R, Galla R, Adepu GS. Development and validation of stability indicating method RP-HPLC method for simultaneous estimation of ivabradin and metoprolol in tablet dosage form. Int J PharmSciRes. 2020; 11(6): 2786-2792.
21. Mohammad YD. Gowri S, Reddy PS. A stability indicating assay method development and validation for simultaneous estimation of Olmesartan Medoxamil and Metoprolol Succinate in bulk and pharmaceutical dosage form by RP-HPLC method. Der Pharmacia Sinica. 2015; 6(7): 21-29.
22. Bidkar JS, Vare SR., Dama GY, Shelke MM, Dhokare AM. Development and Validation of Stability indicating RP-HPLC method for the estimation of metoprolol and ivabradine in solid dosage form. World J Pharm Res; 2019; 8(7): 1742-1768.
23. Govindaraj S, Pamarthi NP, Immadisetty SJ, Dhanapal V. Development and validation of stability indicating RP-HPLC method for simultaneous estimation of metoprolol succinate and clinidipine in bulk and pharmaceutical dosage form. Int J Pharm Pharm Sci. 2015; 7(1): 150-154.
24. Madhukar A, Kannappan N. RP-HPLC method for the simultaneous estimation of cilnidipine and metoprolol succinate in bulk and tablet dosage form in biorelevant media (FaSSIF). Int J PharmTech Res. 2015; 7(1): 172–84.
25. Phale MD, Hamrapurkar PD. Optimization and establishment of a validated stability-indicating HPLC method for the study of the stress degradation behavior of metoprolol succinate. J AOAC Int. 2010; 93(3): 911–6.
26. Kalisetty S, Reddy ST, Reddy MA, Palnati JB, Rao DV, Manikandan R. Stability indicating reverse phase liquid chromatographic method for the determination of metoprolol succinate in pharmaceutical dosage forms. J Chem Pharm Res. 2012; 4(9):4420–5.
27. Shitole S, Gurjar M, Shah M, Bal G,Pimple S, Patel R. Stability Indicating RP-HPLC Method for Quantitative Estimation of S ( - ) Metoprolol Succinate in Tablet Dosage Form. Am. J. PharmTech Res. 2014; 4(5): 711-721
28. Varma PSRCHNP, Lakshmana AR, Dinda SC. Validated stability-indicating HPLC method for simultaneous determination of amlodipine and metoprolol in bulk drug and pharmaceutical formulations. Int J Res Pharm Chem. 2012; 2(3): 876–84.
29. Shahana. V. P, Gayathri Ramya M, Rajesh A, Kathirvel. S. A Comprehensive Validation Method and Development of RP-HPLC for Simultaneous Estimation of Metoprolol, Telmisartan and Chlorthalidonein Bulk and its Formulation. Asian J. Research Chem. 2018; 11(6): 827-834. doi: 10.5958/0974-4150.2018.00146.3
30. Nawale PS, Shirkhedkar AA, Surana SJ, Patil AS. Normal and reversed-phase HPTLC methods for simultaneous estimation of telmisartan and metoprolol succinate in pharmaceutical formulation. ISRN Anal Chem. 2012; 2012: 1–6.
31. Patole SM, Khodke AS, Potale LV, Damle MC. A validated densitometric method for analysis of atorvastatin calcium and metoprolol tartrate as bulk drugs and in combined capsule dosage forms. J Young Pharm. 2011; 3(1): 55-59.
32. Kunjir VV, Jadhav SB, Purkar AJ, Chaudhari PD. Validated HPTLC method for simultaneous determination of olmesartan medoximil and metoprolol succinate in tablet dosage form. Indian Drugs. 2012; 49(10):13–7.
33. Kolhe MH. Development and Validation of TLC Densitometric method for the stability indicating study of metoprolol succinate and hydrochlorthiazide in tablet dosage form. IAJPS. 2016; 3(5): 429–34.
34. Wankhede SB, Dixit NR, Chitlange SS. Stability indicating HPTLC method for quantitative determination of atorvastatin calcium and metoprolol succinate in capsules. Der Pharm Lett. 2011; 3(1):1–7.
35. Jain PS, Patel MK, Bari SB, Surana SJ. Development and validation of HPTLC method for simultaneous determination of amlodipine besylate and metoprolol succinate in bulk and tablets. Indian J Pharm Sci. 2012; 74(2): 152–6.
36. Shailesh Dadge, Chaitali Dhale, Savita Yadav, Janhavi Rao. Stability Indicating HPTLC Method for Estimation of Metoprolol Tartrate in Bulk and in Pharmaceutical Formulation. Asian J. Research Chem. 2018; 11(4):755-762. doi: 10.5958/0974-4150.2018.00133.5
37. Dhale C, Joshi S, Shete S. Development and Validation of spectrophotometric method for determination of metoprolol tartrate. J Applied Pharm. 2014; 6(3):280-285.
38. Chitlange SS, Imra MD, Wankhede SB, Sakarkar DM. Simultaneous estimation of metoprolol and amlodipine from tablet dosage form. Research J. Pharm. and Tech. 2008; 1(2):1-3
39. Yan L, Xiang L, Chunjuan Y, Sheng T, Xiangning Z, Gaefeng L.UPLC–MS-MS Method for Simultaneous Determination of Caffeine, Tolbutamide, Metoprolol, and Dapsone in Rat Plasma and its Application to Cytochrome P450 Activity Study in Rats. J Chromatographic Sci. 2013; 51(1):26-32
40. Sjoukje PK, Jan PY, Gerard H, Sikke K, Bob W, Eric N. A validated high-resolution accurate mass LC-MS assay for quantitative determination of metoprolol and alpha-hydroxymetoprolol in human serum for application in pharmacokinetics. J Applied Bioanalysis. 2017; 3(3): 49-57.
41. Hitanshi Darji, Zarna Dedania, Simultaneous estimation of Azelnidipine and Metoprolol succinate with greenness assessment using HPLC and UV-spectrophotometric methods. Green Analytical Chemistry. 2023; 7: 100079.
42. Nirmala Rangu et al Formulation and Evaluation of Metoprolol Orodispersible Tablets by Super Disintegration Method. Asian J. Pharm. Res. 2018; 8(3): 119-124. doi: 10.5958/2231-5691.2018.00021.7
43. Sojitra Rajanit, ViraniParas, Hashumati Raj. Absorption Correction Method for Simultaneous Estimation of Nifedipine and Metoprolol Succinate in Their Synthetic Mixture Using From Spectrophotometry. Asian J. Pharm. Tech. 2015; 5(1): 13-16. doi: 10.5958/2231-5713.2015.00003.3
44. T. E. Gopala Krishna Murthy, V. Akash. Development of Metoprolol Tartrate Sustained Release Formulations by using Modified Starches. Asian J. Res. Pharm. Sci. 2018; 8(4): 241-246. doi: 10.5958/2231-5659.2018.00040.1
45. Kasad Pinaz A, K.S. Muralikrishna. Base Degradation Study and Method Development of Rivaroxaban by RP-HPLC in bulk. Asian J. Pharm. Res. 2013; 3(3): 109-113
46. Gopal Prasad Agrawal. Validated Stability Indicating Method for Determination of Indapamide in Pharmaceutical Formulation. Research Journal of Pharmacy and Technology. 2021; 14(6): 3347-2
47. Prajakta H Patil, B. M. Gurupadayya, P. D. Hamrapurkar. Stability Indicating HPTLC Determination of Tadalafil Hydrochloride in Bulk Drug and Pharmaceutical Formulations. Research J. Pharm. and Tech. 2020; 13(6): 2608-2614.
48. Vandana S. Bhavnani, Padmanabh B. Deshpande, Santosh V. Gandhi, Prajakta Pawar, Ashish K. Gaikwad, “High Performance Thin Layer Chromatographic Determination of Metoprolol Succinate and Olmesartan in Combined Capsule Dosage Form” Research Journal of Pharmacy and Technology, 2012; 5(11): 1461-1464.
49. Abhijit D. Dhiware, Padmanabh B. Deshpande, Santosh V. Gandhi, Sujith Nair, Suvarna Vanjari. A Simple and Sensitive RP-HPLC method for Simultaneous Estimation of Atorvastatin Calcium, Ezetimibe and Fenofibrate in Combined Tablet Dosage Form. Research Journal of Pharmacy and Technology. 2013; 6(10): 1085-1088.
50. Lata P. Kothapalli, Karan S. Vighne, Rabindra K. Nanda, Asha B. Thomas. Development and Validation of a Stability Indicating HPTLC Method for Estimation of Artemether in Bulk and Formulated dosage form. Asian J. Research Chem. 2015; 8(10): 635-642.
51. Sushil D. Patil, Prajkta Varpe, Sayali Chaure, Siddharth B. Bhalerao, Sanjay Kshirsagar. Development and Validation of Stability Indicating RP-HPLC Method for Piracetam. Asian J. Res. Pharm. Sci. 2017; 7(4):215-221
52. B. Bhavya, P. Nagaraju, V. Mounika, G. Indira Priyadarshini. Stability Indicating RP-HPLC Method Development and Validation for Simultaneous Estimation of Albendazole and Ivermectin in Pharmaceutical Dosage form. Asian J. Pharm. Ana. 2017; 7(1): 6-14.
53. Vanita P. Rode, Madhukar R. Tajne. A Validated Stability-Indicating High-Performance Thin-Layer Chromatographic Method for the Analysis of Pitavastatin in Bulk Drug and Tablet Fomulation. Asian J. Pharm. Ana. 2018; 8(1): 49-52.