DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC FOR DETERMINATION OF ATORVASTATIN CALCIUM and EZETIMIBE IN BULK AND PHARMACEUTICAL DOSAGE FORMS
Objective: A simple, speciï¬c, sensitive, accurate and precise stability indicating methods were described for the quantitative determination of the lipid-lowering agent drug Atorvastatin calcium and Ezetimibe.
Methods: The method was high performance liquid chromatographic with the use of a reversed phase Grace C-18 column (250 mm x 4.66 mm, i.d. 5 Âµm) and a mobile phase of buffer: acetonitrile (60:40 v/v) at a ï¬‚ow rate of 1.0 ml/min.
Results: The retention time of drug was found to be 6.91 min. and 10.31 min, respectively. Quantiï¬cation of the drug was achieved with UV detection at 240 nm. Linear calibration curve was obtained in concentration range 2â€“12 Âµg/ml for both drugs, with r2value of 0.9992 and 0.9990. The limit of detection and limit of quantiï¬cation were found to be 0.81 Âµg/ml and 2.47 Âµg/ml respectively for Atorvastatin calcium and 0.76 Âµg/ml and 2.31 Âµg/ml respectively for Ezetimibe.
Conclusion: The developed methods were successfully validated as per International Conference on Harmonization guideline (ICH). Atorvastatin calcium and Ezetimibe was subjected to different stress conditions. Stress samples were successfully assayed by developed high performance liquid chromatographic and high-performance thin layer liquid chromatographic method. Statistically, analysis proves that there were no statistically signiï¬cant differences between two developed methods.
Keywords: RP-HPLC, Atorvastatin calcium, Ezetimibe, Stability indicating, Validation
2. Dixit RP, Barhate, Nagarsenker MS. Stability indicating RP-HPLC method for simultaneous determination of simvastatin and ezetimibe from tablet dosage form. Indian J Pharm Sci 2010;72:204â€“10.
3. Lofty HM, hegaz MA. Quantitative analysis of ezetimibe and simvastatin in pure powder, binary mixtures and a combined dosage form by spectrophotometry. J AOAC Int 2010;93:1844-55.
4. Patil UP, Gandhi SV, Senger MR, Rajmane VS. A validated densitometric method for analysis of telmisartan and atorvastatin calcium in fixed dose combination. J Chil Chem Soc 2010;55:94-6.
5. Patole SM, Khodke AS, Patole LV, Damle C. A validated HPTLC method for analysis of atorvastatin calcium and metoprolol as bulk drugs and in combined capsule dosage forms. J Young Pharm 2011;3:55-9.
6. Rajput SJ, Rajput HA. Simultaneous spectroscopic estimation of ezetimibe and simvastatin in tablet dosage forms. Indian J Pharm Sci 2007;69:683-6.
7. Singh S, Singh B, Bahuguna R, Wadhwa L, Saxena R. Stress degradation studies on ezetimibe and development of a validated stability-indicating HPLC assay. J Pharm Biomed Anal 2006;41:1037â€“40.
8. Sistla R, Tata VSSK, Kashyap YV, Chandrasekhar D, Diwan PV. Development and validation of a RP-HPLC method for the determination of ezetimibe in pharmaceutical dosage forms. J Pharm Biomed Anal 2005;39:517â€“22.
9. Wang L, Asgharnejad M. Second derivative UV spectrometric determination of atorvastatin calcium in tablet dosage form. J Pharm Biomed Anal 2000;21:1243-8.
10. ICH, Q2A Text on Validation of Analytical Procedures, International Conference On Harmonization, Geneva; 1994. p. 1-5.
11. ICH, Stability Testing of New Drug Substances and Products (Q1AR2), International Conference on Harmonization, IFPMA, Geneva; 2003.