• NITIN MAHAJAN Post Graduate and Research Centre, Department of Chemistry, Maulana Azad College of Arts, Science and Commerce, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, 431001, India
  • SUPARNA DESHMUKH Department of Chemistry, S. K Gandhi college, Kada, Tal: Asthi, Dist: Beed, Maharashtra, 414202, India
  • MAZAHAR FAROOQUI Department of Chemistry, S. K Gandhi college, Kada, Tal: Asthi, Dist: Beed, Maharashtra, 414202, India



Carvedilol, Method development, Validation, Impurities, Related substances, ICH guidelines


Objective: The aim of the research work to develop a simple, sensitive, rugged, robust and specific novel gradient stability indicating reverse phase HPLC method for quantitative determination of known and unknown impurities profiling of Carvedilol pharmaceutical dosage forms (Tablets).

Methods: Chromatographic separation has been achieved on an Inertsil ODS 3V column (150 mm x 4.6 mm, 5μm) with mobile phase consisting Mobile phase-A (Water, Acetonitrile and Trifluroacetic acid in the ratio of 80:20:0.1 v/v/v respectively and pH adjusted to 2.0 with dilute potassium hydroxide solution) and Mobile phase-B (Water and acetonitrile in the ratio of 100:900 v/v respectively) delivered at flow rate of 1.0 ml min-1 and the detection wavelength 240 nm. The column compartment temperature maintained at 40 °C.

Results: Resolution between Carvedilol and its impurities has been achieved greater than 1.5. The developed method was validated as per ICH guidelines. Analytical method found Precise, Linear, accurate, specific, rugged and robust.

Conclusion: Developed and validated novel analytical method can be used to for impurity profile analysis of Carvedilol Pharmaceutical dosage form (Tablets).


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FDA Approved Drug Products: Carvedilol Oral Tablets. Available from: drugsatfda_docs/label/2017/020297s038lbl.pdf. [Last accessed on 02 Jul 2021]

FDA Approved Drug Products: Carvedilol Oral Extended Release Capsules. Available from: [Last accessed on 02 Jul 2021]

Nakamura K, Kusano K, Nakamura Y, Kakishita M, Ohta K, Nagase S, Yamamoto M, Miyaji K, Saito H, Morita H, Emori T, Matsubara H, Toyokuni S, Ohe T. Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation. 2002 June 18;105(24):2867-71. doi: 10.1161/ 01.cir.0000018605.14470.dd, PMID 12070115.

Kukin ML, Kalman J, Charney RH, Levy DK, Buchholz Varley C, Ocampo ON, Eng C. Prospective, randomized comparison of effect of long-term treatment with metoprolol or carvedilol on symptoms, exercise, ejection fraction, and oxidative stress in heart failure. Circulation. 1999;99(20):2645-51. doi: 10.1161/01.cir.99.20.2645, PMID 10338457.

Varin F, Cubeddu LX, Powell JR. Liquid chromatographic assay and disposition of carvedilol in healthy volunteers. J Pharm Sci. 1986;75(12):1195-7. doi: 10.1002/jps.2600751218, PMID 3559930.

Vander off BT, Ruppel HM, Amsterdam PB. Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Phys. 1998;58:1627-34.

Nichols AJ, Gellai M, Ruffolo RR. Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundam Clin Pharmacol. 1991;5(1):25-38. doi: 10.1111/j.1472-8206.1991.tb00698.x, PMID 1712335.

Ruffolo RR, Gellai M, Hieble JP, Willette RN, Nichols AJ. The pharmacology of carvedilol. Eur J Clin Pharmacol. 1990;38;Suppl 2:S82-8. doi: 10.1007/BF01409471, PMID 1974511.

Morgan T. Clinical pharmacokinetics and pharmacodynamics of carvedilol. Clin Pharmacokinet. 1994 May;26(5):335-46. doi: 10.2165/00003088-199426050-00002, PMID 7914479.

Gorog S, Babjak M, Balogh G, Brlik J, Csehi A, Dravecz F, Gasdag M, Horvath P, Lauko A, Varga K. Drug impurity profiling strategies. Talanta. 1997;44(9):1517-26. doi: 10.1016/S0039-9140(96)02179-0, PMID 18966892.

International Conference on Harmonization (ICH) Q3A (R2): Impurities in New Drug substance; 2006.

International Conference on Harmonization (ICH) Q3B (R2): Impurities in New Drug Products; June 2006.

FDA. Guidance for industry, analytical procedures and method validation for drug and biologics. United States Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER); July 2015.

Bakshi M, Singh S. Development of validated stability-indicating assay methods-critical review. J Pharm Biomed Anal. 2002;28(6):1011-40. doi: 10.1016/s0731-7085(02)00047-x, PMID 12049968.

Swartz M, Krull I. Analytical method validation for biotechnology proteins, peptides and antibodies. LC GC North Am. 2009;27(7):550-75.

International Conference on Harmonization (ICH) Q2 (R1): Validation of Analytical Procedures Test and Methodology; November 2005.

Epshtein NA. Validation of HPLC techniques for pharmaceutical analysis. Pharm Chem J. 2004;38(4):212-28. doi: 10.1023/B:PHAC.0000038422.27193.6c.

Abdullah JW, Shariq H, Siddiqui JA. Method development and analytical method validation of carvedilol by high-performance liquid chromatography. J Pharm Biol Sci. 2016;11(6):93-7.

Ciobanu AM, Pop A, Crisan S, Pali M, Burcea-Drag G, Popa D. HPLC studies for assessing the stability of carvedilol tablets. Farmacia. 2017;65(4):523.

Savic I, Marinkovc V, Savic I, Sibinovic P, Cekic N. Application of the experimental design method to photostability studies of Karvileks tablet. Indian J Pharm Educ Res. 2012;43(3):275-82.

Sripalakit P, Kaewnok S, Tubtonglang S. Development of carvedilol assay in tablet dosage form using HPLC with fluorescence detection. Maejo Int J Sci Technol. 2010;4(01):8-19.

Mahaveer S, Kashkhedikar SG, Love S, Garg A, Tripti G, Patel A. Development of RP-HPLC method for estimation of carvedilol in tablet formulations. Res J Pharm Technol. 2008;1:1.

Uma V, Rao M, Haritha G, Krishnaiah T, Gouri T, Saikiran. Method development and forced degradation studies of carvedilol by RP-HPLC. Int J Pharm Anal Res. 2017;6(3):457-68.

Desai DC, Karkhanis VV. Simple spectrometric estimation of carvedilol phosphate in bulk and tablet dosage form. Int Res J Pharm. 2012;3(2).

Dey S, Kumar D, Sreenivas SA, Sandeep D. Analytical method development and validation of carvedilol by HPLC in bulk and dosage form. J Pharm Res. 2010;3(12):3075.

Patel LJ, Suhagia BN, Shah PB, Shah RR. RP-HPLC and HPTLC methods for the estimation of carvedilol in bulk drug and pharmaceutical formulations. Indian J Pharm Sci. 2006;68(6):790. doi: 10.4103/0250-474X.31017.

Myung SW, Jo CH. Gas chromatograph-mass spectrometric method for the determination of carvedilol and its metabolites in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;822(1-2):70-7. doi: 10.1016/j.jchromb.2005.05.023, PMID 15996536.

Hossain MD, Kundu DR, Sharmin T, Maleque M, Chowdhury SR. A simple reversed phase high-performance liquid chromatography method development and validation for determination of carvedilol in pharmaceutical dosage forms. Int J Adv Pharm Anal. 2013;3:68-71.

Nadella NP, Ratnakaram VN, Srinivasu N. Development and validation of UPLC method for simultaneous quantification of carvedilol and ivabradine in the presence of degradation products using DoE concept. J Liq Chromatogr Relat Technol. 2018;41(3):143-53. doi: 10.1080/10826076.2018.1427595.

Mali AD. Simultaneous determination of carvedilol and hydrochlothiazide in pharmaceutical dosage form by first order derivative UV spectrophotometry. Int J Pharm Sci. 2015;7(9):371-4.

Sajan PG, Rohith T, Patil P, Mantelingu K, Rangappa KS, Kumar MN. Rapid highly efficient and stability indicating RP-HPLC method for the quantitative determination of potential impurities of carvedilol active pharmaceutical ingredient. Int J Pharm Pharm Sci. 2014;6(10):214-20.

Stojanovic J, Marinkovic V, Vladimirov S, Velickovic D, Sibinovic P. Determination of carvedilol and its impurities in pharmaceuticals. Chromatographia. 2005;62(9-10):539-42. doi: 10.1365/s10337-005-0656-y.

Kang TC, GU, Xiao HE, Jia-jia. Determination of impurities D and E of carvedilol tablets by RP-HPLC. Chin J Pharm Anal. 2015;35(10):1838-42.

Raju TVR. Development and validation of stability-indicating impurity profiling method for the carvedilol in API and pharmaceutical formulation. Int J Pharmacol Pharm Sci. 2015;2(6):22-31.

Eisenberg EJ, Patterson WR, Kahn GC. High-performance liquid chromatographic method for the simultaneous determination of the enantiomers of carvedilol and its O-desmethyl metabolite in human plasma after chiral derivatization. J Chromatogr B. 1989;493:105-15. doi: 10.1016/S0378-4347(00)82713-9.



How to Cite

MAHAJAN, N., S. DESHMUKH, and M. FAROOQUI. “ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR KNOWN AND UNKNOWN IMPURITIES PROFILING FOR CARVEDILOL PHARMACEUTICAL DOSAGE FORM (TABLETS)”. International Journal of Current Pharmaceutical Research, vol. 13, no. 6, Nov. 2021, pp. 71-80, doi:10.22159/ijcpr.2021v13i6.1922.



Original Article(s)