A Validated Stability Indicating RP-UPLC Method for Atrovastain Calcium

Kakumani Kishore Kumar, Chimalakonda Kameswara Rao, Maddala Vijaya Lakshmi, Khagga Mukkanti

Centre for Chemical Sciences and Technology, Institute of Science and Technology, JNT University, Hyderabad, India.
Centre for Chemical Sciences and Technology, Institute of Science and Technology, JNT University, Hyderabad, India..

DOI: 10.4236/ajac.2012.35052                

Abstract

The present paper describes stability indicating reverse phase Ultra performance liquid chromatographic (RPLC) assay method for Atrovastatin Calcium in bulk drugs. The developed method is also applicable for the related substance determination and degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of acid hydrolysis, base hydrolysis, oxidation, photolysis and thermal degradation. The degradation of Atrovastatin was observed under acid hydrolysis, base hydrolysis and peroxide hydrolysis. The drug was found to be stable to other stress conditions attempted. Successful separation of the drug from synthetic impurities and degradation product formed under stress conditions was achieved on a C18 column using buffer 0.02 M phosphoric acid and acetonitrile. The developed UPLC method was validated with respect to linearity, accuracy, precision, specificity and ro-bustness. The developed UPLC method to determine the related substances and assay determination of Atrovastatin can be used to evaluate the quality of regular production samples. It can be also used to test the stability sample of Atrovastatin Calcium.

Keywords

Stability Indicating Study; Atrovastatin Calcium; Liquid Chromatography and Impurities

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. L. Witzum, “Drug Used in the Treatment of Hyperlipopro-teinemias,” 9th Edition, Mc Graw Hill, New york, 1996.
[2]	L. Posvar, L. L. Radulovic, D. D. Cilla, et al., “To-larance and Pharmacokinetics of Signal-Dose Atrovastatin, a Potent Inhibitor of HMG-CoA Reductase, in Health Subjects,” The Journal of Clinical Pharmacology, Vol. 36, No. 8, 1996, pp. 728-731.
[3]	S. Budavari, “The Merck Index, an Ency-clopaedia of Chemicals, Drugs and Biologicals,”13th Edition, Merck, White House Station, 2001.
[4]	T. G. Altuntas and N. Erk, “Liquid Chromatographic Determination of Atorvastatin in Bulk Drug, Tablets, and Human Plasma,” Journal of Liquid Chromatography & Related Technologies, Vol. 27, No. 1, 2004, pp. 83-93. doi:10.1081/JLC-120027087
[5]	M. K. Pasha, S. Muzeeb, S. J. S. Basha, D. Shashikumar, R. Mullangi and N. R. Srinivas, “Analysis of Five HMG- CoA Reductase Inhibi-tors—Atorvastatin, Lovastatin, Pra-vastatin, Rosuvastatin and Simvastatin: Pharmacological, Pharmacokinetic and Analytical Overview and Development of a New Method for Use in Pharmaceutical Formulations Analysisand In Vitro Metabolism Studies,” Biomedical Chromatography, Vol. 20, No. 3, 2006, pp. 282-293. doi:10.1002/bmc.561
[6]	U. Seshachalam and C. B. Kothapally, “HPLC Analysis for Simultaneous Determination of Atorvastatin and Ezetimibe in Pharmaceutical Formulations,” Journal of Liquid Chromatography & Related Technologies, Vol. 31, No. 5, 2008, pp. 714-721. doi:10.1080/10826070701854402
[7]	S. Erturk, E. S. Aktas, L. Ersoy and S. Ficicioglu, “An HPLC Method for the Determination of Atorvastatin and Its Impurities in Bulk Drug and Tablets,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 33, No. 5, 2003, pp. 1017-1023. doi:10.1016/S0731-7085(03)00408-4
[8]	R. Nirogi, K. Mudigonda and V. Kandikere, “Chromatography-Mass Spectrometry Methods for the Quantification of Statins in Biological Samples,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 44, No. 2, 2007, pp. 379-387. doi:10.1016/j.jpba.2007.02.008
[9]	L. Novakova, D. Satinsky and P. Solich, “HPLC Methods for the Determination of Sim-vastatin and Atorvastatin,” TrAC Trends in Analytical Chemistry, Vol. 27, No. 4, 2008, pp. 352-367.
[10]	M. Bakshi and S. Singh, “Development of Validated Stability-Indicating Assay Methods—Critical Review,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 28, No. 6, 2002, pp. 1011-40. doi:10.1016/S0731-7085(02)00047-X
[11]	CPMP/ICH/281/95, “Note for Guidance on Validation of Analytical Procedure: Methodology, ICH Topic Q2B Validation of Analytical Procedure: Methodology, Step 4,” 1996. www.ich.org.
[12]	CPMP/ICH/381/95, “Note for Guidance on Validation of Analytical Method: Definition and Terminology, Step 5,” 1994. www.ich.org.