A NEW STABILITY-INDICATING RP-HPLC-PDA METHOD FOR SIMULTANEOUS ESTIMATION OF TRIPLICATE MIXTURE OF RAMIPRIL, ATORVASTATIN AND CLOPIDOGREL IN TABLET DOSAGE FORM
Objective: To develop a novel, accurate, precise and linear reverse phase high performance liquid chromatographic (RP-HPLC) method for simultaneous quantitative estimation of ramipril, atorvastatin and clopidogrel in Atamra-CV tablet and validate as per international conference on harmonization (ICH) guidelines and to perform the force degradation studies using the developed method.
Methods: In the present work, the good chromatographic separation was achieved isocratically using a shim-pack HPLC Kromasil 150 mm x 4.6 mm, 5 m. m. And mobile phase consisting of 0.05 M potassium dihydrogen orthophosphate pH 3 adjusted with orthophosphoric acid and acetonitrile in the ratio (52:48), at flow rate 1 ml/min and column temperature (30 Â°C). The effluents obtained were monitored at 210 nm with the UV-visible detector.
Results: The retention time of ramipril, atorvastatin and clopidogrel was found to be 2.893 min, 5.012 min and 6.102 min respectively. The linearity of ramipril, atorvastatin and clopidogrel was found in the range of 25-150 % and the correlation coefficient for ramipril, atorvastatin and clopidogrel were>0.999. The high recovery values (98%-101%) indicate a satisfactory accuracy. The low percent relative standard deviation (% RSD) values in the precision study reveals that the method is precise. The three-drug samples were subjected to stress conditions of acidic and alkaline hydrolysis, oxidation, photolysis and thermal degradation. The proposed method proved to be stability-indicating by resolution of the analytes from their forced-degradation products.
Conclusion: The developed method is novel, simple, precise, rapid, accurate and reproducible for simultaneous estimation of ramipril, atorvastatin and clopidogrel tablet dosage form. Hence the proposed method may find practical applications as a quality-control tool in the simultaneous analysis of the three drugs in combined dosage forms in quality-control laboratories. The proposed method was made use of photodiode array (PDA) as a tool for peak identification and purity confirmation.
2. Warner TG, Perry MC. Ramipril: a review of its use in the prevention of cardiovascular outcomes. Drugs 2002;62:1381â€“405.
3. Andal NJK, Mohangandhi B, Bhaskararaju V, Srinivassumanth K, Venkatakoteswaramma K, Srinivas K, et al. Development and validation of stability indicating RP-HPLC method for simultaneous estimation of ramipril, aspirin and simvastatin in bulk and pharmaceutical dosage form. Asian J Biomed Pharm Sci 2016;6:14-20.
4. Vaibhav R, Amrita S, Varsha K. Method development and validation of fast dissolving tablet of ramipril by HPLC method. Int J Pharm Sci 2016;8:174-8.
5. Indian Pharmacopoeia. The controller of publication Govt. of India, New Delhi; 2007.
6. Patole SM, Potale1 LV, Khodke AS, Damle MC. Validated HPLC method for analysis of atorvastatin calcium, ramipril and aspirin as the bulk drug and in combined capsule dosage forms. Int J Pharma Sci Rev 2010;4:40-5.
7. Rajesh S, Sunil K, Ganesh PM. Development and Validation of RP-HPLC method for simultaneous estimation of ramipril, aspirin and atorvastatin in pharmaceutical preparations. E J Chem 2012;9:2177-84.
8. Kamatchi Sankar AS, Thangarasu V, Venkappaya D. Simultaneous estimation of ramipril, acetylsalicylic acid and atorvastatin calcium by chemometrics assisted UV-spectrophotometric method in capsules. Acta Pharm 2011; 61:283-96.
9. Patel RB, Shankar MB, Patel MR, Bhatt KK. Simultaneous estimation of acetylsalicylic acid and clopidogrel bisulfate in pure powder and tablet formulations by high-performance column liquid chromatography and high-performance thin-layer chromatography. J AOAC Int 2008;91:750-5.
10. Jinesh Bahubali N, Preethi Anantharaju G. Analytical RP-HPLC method development and validation for the simultaneous estimation of ramipril and hydrochlorothiazide in tablet dosage form. Am J PharmTech Res 2014;4:349-65.
11. Budavari, O'Neil, Maryadele J. The merck index an encyclopedia of chemicals, drugs and biologicals. 13th ed. Whitehouse Station: N. J Merck; 2001.
12. Noha I, Mohamaed R, Ahmed I, Shereen T, Inas Ali. Simultaneous determination of amlodipine besylate and atorvastatin calcium by using spectrophotometric method with multivariate calibration and HPLC method implementing â€œ design of experimentâ€. Int J Pharm Sci 2014;6:419-25.
13. Indian Pharmacopoeia: Published by the Controller of Publications. Government of India, Ministry of Health and Family Welfare. Volume I and II. Delhi; 1996.
14. Indian Pharmacopoeia: Ministry of Health and Family Welfare, The Indian Pharmacopoeia commission. Volume I and II. New Delhi: Published by the Government of India; 2007. p. 131, 1036.
15. Martindale: The Complete Drug Reference. 36th edition. London: Pharmaceutical Press; 2009. p. 20, 1218.
16. Budavari S. The Merck Index. 12th ed. White House Station (New Jersey): Merck and Co., Inc.; 1996. p. 146.
17. Reynolds EF, Dale M. The extra pharmacopoeia. 31st ed. London (Britain): Royal Pharmaceutical Society; 1996. p. 1302.
18. Gurupadayya GM, Sindhura S. Bio-analytical determination of clopidogrel and pantoprazole by RP-HPLC method in rat plasma: application to drug interaction study. Asian J Pharm Clin Res 2014;7:10-3.
19. Kim DS, Lee BJ, Yong YJ, Kim JO. Comparison of a solid SMEDDS and solid dispersion for enhanced stability and bioavailability of clopidogrelnapadisilate. J Carb Pol 2014;114:365â€“74.
20. Marta K, Dorota D, Artur T, CzesÅ‚aw Z, Gilles T. HPLCâ€“MS/MS method for the simultaneous determination of clopidogrel, its carboxylic acid metabolite and derivatized isomers of thiol metabolite in clinical samples. J Chromatogr B 2012;911:105â€“12.
21. Neela M, Bhatiaa, Gurava SB, Swapnil D, Jadhava, Manish. RP-HPLC method for simultaneous estimation of atorvastatin calcium, losartan potassium, atenolol, and aspirin from tablet dosage form and plasma. J Liq Chromatogr Relat Technol 2012;35:428-43.
22. Durgarao D, Kalyanaraman L, Sait SS, Venkata Rao P. A validated stability-indicating normal phase LC method for clopidogrel bisulfate and its impurities in bulk drug and pharmaceutical dosage form. J Pharm Biomed Anal 2010;52:160â€“5.
23. Sheshadri R. Simultaneous quantitative determination of metroprolol, atorvastatin and ramipril in capsules by a validated stability indicating RP-UPLC method. Sci Pharm 2010;78:821-34.
24. Kamatchi Sankar AS, Thangarasu V, Venkappaya D. Simultaneous estimation of ramipril, acetylsalicylic acid and atorvastatin calcium by chemometrics assisted UV-spectrophotometric method in capsules. Acta Pharm 2011;61:283-96.
25. ICH, Stability testing of new drug substances and products (Q1AR2), International Conference on Harmonization, IFPMA, Geneva; 2003.
26. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use. Validation of Analytical Procedures: Text and Methodology ICH Q2 (R1); 2005.
27. ICH guidelines for impurities in new drug substances Text and methodology Q3A (R2), International Conference on Harmonization; 2006.
28. Nitin D, Manju P, Dinesh KJ. Simultaneous estimation of aspirin, atorvastatin and clopidogrel in combined capsule dosage form using reverse phase high-performance liquid chromatography. Int J Pharm Biomed Pharm Sci 2013;7:42-4.
29. Sahityasundar R, Valliappan K. New stability indicating assay method by liquid chromatographic separation of aspirin, atorvastatin and clopidogrel in pharmaceutical dosage form. Indo Am J Pharm Res 2014;4:1519-27.