RAPID, HIGHLY EFFICIENT AND STABILITY INDICATING RP-UPLC METHOD FOR THE QUANTITATIVE DETERMINATION OF POTENTIAL IMPURITIES OF CARVEDILOL ACTIVE PHARMACEUTICAL INGREDIENT
Keywords:Carvedilol, Impurities, RP-UPLC, Validation, Forced degradation
Objective: The main objective of the proposed study was to develop a sensitive, rapid and stability indicating reverse phase UV-UPLC method for the quantitative determination of potential impurities in carvedilol.
Methods: The chromatographic separations were achieved on waters Acquity UPLC BEH C18 column (100 mm length 2.1 mm ID with 1.7 Âµm particle size, Waters corporation, MA, USA). Mobile phase A consisted, 0.04% trifluroacetic acid in water and mobile phase B consisted as 0.04% trifluroacetic acid in acetonitrile with a gradient programme (Tmin A:B) T090:10, T465:35, T740:60, T1020:80, T10.1 90:10. The column temperature was maintained at 60 Â°C and the detection was carried out at 240 nm. The flow rate was set to 0.5 mL/min.
Results: Efficient chromatographic separation was achieved on UPLC BEH C18 stationary phase in gradient mode using simple mobile phase. In forced degradation study, major degradation of the drug substance was found to occur under oxidative stress conditions to form carvedilol hydroxylamine. The method was validated according to ICH guidelines with respect to specificity, precision, linearity and accuracy. Regression analysis showed the correlation coefficient value greater than 0.999 for carvedilol and its five impurities. Detection limit of impurities was in the range of 0.002â€“0.004% indicating the high sensitivity of the newly developed method. Accuracy of the method was established based on the recovery obtained between 96.7% and 108.1% for all impurities.
Conclusion: A new, rapid and highly efficient UPLC method was developed, which separates all impurities and degradation products of carvedilol. The method has been validated in order to ascertain the suitability and stability indicating power of the method.
F Varin, LX Cubeddu, JR Powell. Liquid chromatographic assay and disposition of carvedilol in healthy volunteers. J Pharm Sci 1986;75:1195-7.
Vanderhoff BT, Ruppel HM, Amsterdam PB. Carvedilol: the new role of beta blockers in congestive heart failure. Am Family Physician 1998;58:1627-34.
Nichols AJ, Gellai M, Ruffolo. Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundamental Clinical Pharmacol 1991;5:25-38.
Ruffolo RR, Gellai M, Hieble JP, Willette RN, AJ Nichols. The Pharmacology of carvedilol. Eur J Clinical Pharm 1990;38:82-8.
GM Keating, B Jarvis. Carvedilol: a review of its use in chronic heart failure. Drugs 2003;63:1697-741.
TW Gehr, DM Tenero, DA Boyle, Y Qian, DA Sica, NH Shusterman. The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency. Eur J Clinical Pharm 1999;55:269-77.
N Hokama, N Hobara, H Kameya, S Ohshiro, M Sakanashi. Rapid and simple micro-determination of carvedilol in rat plasma by high-performance liquid chromatography. J Chromatography 1999;732:233-8.
European Pharmacopoeia 2011:1193-4.
Unites States Pharmacopoeia. Revision Bull 2011.
P Ptacek, J Macek, J Klima. Liquid chromatographic determination of carvedilol in human plasma. J Chromatography 2003;789:405-10.
Md. Amran hossain, Dipu Rani Kundu, Tasnuva Sharmin, Mahfuza Maleque, Sharmin Reza Chowdhury. 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.
J Stojanovoic, V marinkovic, S Vladimirov, D Velickovic, P Sibinovic. Determination of carvedilol and its impurities in pharmaceuticals. J Chromatographia 2005;62:539-42.
P Ajit, M Hate, L Godwin, B Sudesh, A Amjad, T Janardhan, et al. Method development and validation of carvedilol and its impurities by RP-HPLC. Int J Pharm Sci 2012;4:1908-15.
Subhashini Edla, B Syama Sundhar. RP-HPLC method development and validation for the analyisis of carvedilol in pharmaceutical dosage forms. Int J Sci Innovations Discoveries 2011;1:433-40.
Mohammad Rizwan, Mohammed Aqil, Adnan Azeem, Yasmin Sultana, Sushama Talegaonkar, Asgar Ali. Study of the degradation kinetics of carvedilol by use of a validated stability-indicating lc method. J Chromatographia 2009;70:1283-6.
Lucie NovÂ´akovÂ´a, Ludmila MatysovÂ´a, Petr Solich. Advantages of application of UPLC in pharmaceutical analysis. Talanta 2006;68:908â€“18.
Olga Galanopouloua, Stavroula Rozoub, Ekaterini Antoniadou Vyzaa. HPLC analysis, isolation and identification of a new degradation product in carvedilol tablets. J Pharm Biol Anal 2008;48:70â€“7.
International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use. Validation of Analytical Procedures: Methodology. ICH-Q2 (R1); 2005.