Author(s):
Rutuja U. Gaikwad, Amit S. Tapkir, Nagesh R. Wadikar, Shejal K. Wakade, Ashok B. Pathak, Sandip M. Bhagat
Email(s):
amittapkir.8@gmail.com
DOI:
10.52711/0974-360X.2025.00162
Address:
Rutuja U. Gaikwad1, Amit S. Tapkir1*, Nagesh R. Wadikar1, Shejal K. Wakade1, Ashok B. Pathak2, Sandip M. Bhagat2
1PES’s, Modern College of Pharmacy, Nigdi, Pune - 44, Maharashtra, India.
2Anasyn Lab Private Limited, Tathawade, Pune - 33, Maharashtra, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 3,
Year - 2025
ABSTRACT:
Metoprolol, characterized by its chemical nomenclature as 1-[4-(2-Methoxyethyl) phenoxy]-3-[(propan-2-yl) amino]propan-2-ol, possesses a mol. weight of 267.3g/mol., is recognized as a selective blocker of the ß1 receptor. It is frequently prescribed for managing hypertension, alleviating chest pain resulting from insufficient Enhancing the circulation of blood to the heart and managing diverse conditions linked to an abnormally elevated heart rate. The objective of the research is to produce essential impurities of metoprolol. In the course of drug development, it is crucial to regulate impurities and ensure they remain within specified limits to achieve high-quality drugs. Numerous studies have been undertaken to synthesize impurities and examine their structures, supporting the purification methods. The integrity of compounds which are synthesized was verified through analyzing the spectral data, including (IR) infrared, (NMR) Nuclear Magnetic Resonance, and (MASS) Mass Spectrometry. Additionally, the purity of these compounds was affirmed through microanalysis.
Cite this article:
Rutuja U. Gaikwad, Amit S. Tapkir, Nagesh R. Wadikar, Shejal K. Wakade, Ashok B. Pathak, Sandip M. Bhagat. Comprehensive Investigation and Exploration of Metoprolol Impurities: Novel Synthesis, Refinement and Characterization. Research Journal Pharmacy and Technology. 2025;18(3):1128-3. doi: 10.52711/0974-360X.2025.00162
Cite(Electronic):
Rutuja U. Gaikwad, Amit S. Tapkir, Nagesh R. Wadikar, Shejal K. Wakade, Ashok B. Pathak, Sandip M. Bhagat. Comprehensive Investigation and Exploration of Metoprolol Impurities: Novel Synthesis, Refinement and Characterization. Research Journal Pharmacy and Technology. 2025;18(3):1128-3. doi: 10.52711/0974-360X.2025.00162 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-3-23
REFERENCES:
1. Maczewski M, Mackiewicz U. Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart. Cardiovascular Research. 2008; Jul 1; 79(1): 42-51. https://doi.org/10.1093/cvr/cvn057.
2. Prabhu SD, Wang G, Luo J, Gu Y, Ping P, Chandrasekar B. β-Adrenergic receptor blockade modulates Bcl-XS expression and reduces apoptosis in failing myocardium. Journal of Molecular and Cellular Cardiology. 2003; May 1; 35(5): 483-93. https://doi.org/10.1016/S0022-2828(03)00052-X.
3. Sabbah HN, Sharov VG, Gupta RC, Todor A, Singh V, Goldstein S. Chronic therapy with metoprolol attenuates cardiomyocyte apoptosis in dogs with heart failure. Journal of the American College of Cardiology. 2000; Nov 1; 36(5): 1698-705. https://doi.org/10.1023/A:1013719821673.
4. Cizmarikova R, Habala L, Valentova J, Markuliak M. Survey of pharmacological activity and pharmacokinetics of selected β-adrenergic blockers in regard to their stereochemistry. Applied Sciences. 2019; Feb 13; 9(4): 625. https://doi.org/10.3390/app9040625.
5. Ye, Q.; Huang, Y.; Rusowicz, A.; Palaniswamy, V.A.; Raglino, T.V. Understanding and controlling the formation of an impurity during the development of muraglitazar, a PPAR dual agonist. Org. Process. Res. Dev. 2010; 14; 238–224. https://doi.org/10.1021/op9002104.
6. Kadivar MH, Sinha PK, Kushwah D, Jana P, Sharma H, Bapodra A. Study of impurity carryover and impurity profile in Febuxostat drug substance by LC–MS/MS technique. Journal of Pharmaceutical and Biomedical Analysis. 2011; Dec 5; 56(4): 749-57. https://doi.org/10.1016/j.jpba.2011.07.039.
7. Bartos D, Gorog S. Recent advances in the impurity profiling of drugs. Current Pharmaceutical Analysis. 2008; Nov 1; 4(4): 215-30. https://doi.org/10.2174/157341208786306199
8. Internation Conference on Harmonization (ICH) Guidelines, Q3A (R2): Impurities in New Drug Substances, March, 2020. Accessed 20 September 2020.
9. Internation Conference on Harmonization (ICH) Guidelines, Q3B (R2): Impurities in New Drug Products, March, 2020. Accessed 20 September 2020.
10. Internation Conference on Harmonization (ICH) Guidelines, Q3C (R8): Impurities guidelines for residual solvents. March, 2020. Accessed 20 September 2020.
11. Pramanik C, Bhumkar R, Karhade G, Khairnar P, Tripathy NK, Gurjar MK. Efficient synthesis of impurity-C of antimigraine agent rizatriptan benzoate. Organic Process Research and Development. 2012; Mar 16; 16(3): 507-11:https://doi.org/10.1021/op200284m.
12. Holam MR, Komala M. Molecular Docking Studies of substituted 3-methyl-4-oxo-sulfanylidene-1, 2, 3, 4-tetrahydropyrimidine-5-carbonitrile derivatives. Research Journal of Pharmacy and Technology. 2023; 16(10): 4825-30. http://dx.doi.org/10.52711/0974-360X.2023.00782.
13. Mali SS, Killedar SG. To Enhance the Physicochemical Properties of Metoprolol Succinate By Co-Crystal Technique. Research Journal of Pharmacy and Technology. 2017; 10(11): 3761-7. http://dx.doi.org/10.5958/0974-360X.2017.00683.7
14. Mujoriya RZ, Singh DC, Gupta VA, Bisen A, Bondre AB. Formulation development and evaluation of metoprolol succinate ER and amlodipine besilate bilayer tablet. Research Journal of Pharmacy and Technology. 2010; 3(4): 1291-4. 10.5958/0974-360X.
15. Gorog S. New safe medicines faster: the role of analytical chemistry. TrAC Trends in Analytical Chemistry. 2003; Jul 1; 22(7): 407-15. https://doi.org/10.1016/S0165-9936(03)00701-5
16. Gandhi NK, Ezhava SB. Stability indicating Analytical Method Development using Quality by Design (QbD) approach for simultaneous estimation of Ivabradine and Metoprolol. Research Journal of Pharmacy and Technology. 2021; 14(11): 5937-44: https://doi.org/10.1093/jaoacint/qsab172
17. Palanisamy M, Khanam J, Kumar NA, Rani C. Chitosan microspheres encapsulated with metoprolol succinate: formulation and in-vitro evaluation. Research Journal of Pharmacy and Technology. 2009; 2(2): 349-52: 10.5958/0974-360X.
18. Younes OM, Ali FA, Assaf ZA. Enantioseparation of Metoprolol Tartrate using HPLC by Adding Methyl beta Cyclodextrin to the mobile Phase (As Chiral Additive). Research Journal of Pharmacy and Technology. 2018; 11(9): 3937-42: 10.5958/0974-360X.2018.00723.0.
19. Haritha G, Aanandhi VM, Shanmugasundaram P. Novel method development for metformin, ivabradine, metoprolol and ertugliflozin and its validation in API and pharmaceutical dosage form by RPHPLC method. Research Journal of Pharmacy and Technology. 2021; 14(4): 2055-61. 10.52711/0974-360X.2021.00365.
20. Kolagani A, Bochu SS, Ganapaneni NM, Gangireddy R. Design and In-vitro evaluation of gastro retentive drug delivery systems of metoprolol succinate. Research Journal of Pharmacy and Technology. 2020; 13(8): 3666-70. 10.5958/0974-360X.2020.00648.4.
21. Verma N, Ghosh AK, Chattopadhyay P. UV-spectrophotometric determination of metoprolol succinate. Research Journal of Pharmacy and Technology. 2011; 4(2): 271-2. 10.5958/0974-360X
22. Raval HV, Patel DM, Patel CN. Estimation of metoprolol tartrate and chlorthalidone in combined dosage form by UV-spectrophotometric methods. Research Journal of Pharmacy and Technology. 2011; 4(7): 1132-4: 10.5958/0974-360X
23. Soni S, Ram V, Verma D, Verma A. Analytical method development and validation of metoprolol succinate by high performance liquid Chromatography and Ultraviolet spectroscopy technique. Research Journal of Pharmacy and Technology. 2021; 14(2): 931-7. 10.5958/0974-360X.2021.00166.9