Degradation Pathway for Pitavastatin Calcium by Validated Stability Indicating UPLC Method

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DOI: 10.4236/ajac.2010.12011   PDF   HTML     8,515 Downloads   18,382 Views   Citations

Abstract

Degradation pathway for pitavastatin calcium is established as per ICH recommendations by validated and stability indicating reverse phase liquid chromatographic method. Pitavastatin is subjected to stress conditions of acid, base, oxidation, thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Four impurities are studied among which impurity-4 is found prominent degradant. The stress samples are assayed against a qualified reference standard and the mass balance is found close to 99.5%. Efficient chromatographic separation is achieved on a BEH C18 stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 245 nm at a flow rate of 0.3 mL min-1. In the developed UPLC method the resolution between pitavastatin calcium and four potential impurities is found to be greater than 4.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.998 for pitavastatin calcium and four potential impurities. This method is capable to detect the impurities of pitavastatin calcium at a level of 0.006% with respect to test concentration of 0.10 mg/mL for a 2-µL injection volume. The developed UPLC method is validated with respect to specificity, linearity & range, accuracy, precision and robustness for impurities determination and assay determination.

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A. Gomas, P. Ram, N. Srinivas and J. Sriramulu, "Degradation Pathway for Pitavastatin Calcium by Validated Stability Indicating UPLC Method," American Journal of Analytical Chemistry, Vol. 1 No. 2, 2010, pp. 83-90. doi: 10.4236/ajac.2010.12011.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] K. Kajinami, N. Takekoshi and Y Saito, “Pitavastatin: Efficacy and Safety Profiles of a Novel Synthetic HMG- CoA Reductase Inhibitor,” Cardiovascular Drug Reviews, Vol. 21, 2003, pp. 199-215.
[2] R. Y. Mukhtar, J. Reid and J. P. Reckless, “Pitavastatin,” International Journal of Clinical Practice, Vol. 59, 2005, pp. 239-252.
[3] N. Satheesh Kumar and J. Baghyalakshmi, “Determination and Quantification of Pitavastatin Calcium in Tablet Dosage Formulation by HPTLC Method,” Analytical Letters, Vol. 40, No. 14, 2007, pp. 2625-2632.
[4] H. J. Panchal, B. N. Suhagia, N. J. Patel and B. H. Patel, “A Simple and Sensitive HPTLC Method for Quantitative Analysis of Pitavastatin Calcium in Tablets,” Journal of Planar Chromatography—Modern TLC, Vol. 21, No. 4, 2008, pp. 267-270.
[5] R. Nirogi, K. Mudigonda and V. Kandikere, “Chromatography–Mass Spectrometry Methods for the Quantitation of Statins in Biological Samples,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 44, No. 2, 2007, pp. 379-387.
[6] J. Z. Shen-Tu, X. Xu, J. Liu, X. J. Hu, J. C. Chen, L. H. Wu, M. Z. Huang and H. L. Zhou, “Determination of Pitavastatin in Human Plasma by LC–MS–MS,” Chromatographia, Vol. 69, No. 9-10, 2009, pp. 1041-1047.
[7] ICH, “Stability Testing of New Drug Substances and Products”, Q1A(R2), 2005.
[8] ICH, “Photo stability Testing of New Drug Substances and Products,” Q1B, 2005.
[9] S. W. Baertschi, K. Alsante and R. A. Reed, “Pharmaceutical Stress Testing: Predicting Drug Degradation,” Informa Healthcare, 2005.
[10] US FDA Guidance, “Analytical Procedures and Methods Validation,” 2000.
[11] Validation of Compendial Methods <1225>, “The United States Pharmacopeia,” 2009.
[12] M. E. Swartz and I. S. Krull, “Developing and Validating Stability-Indicating Methods,” Pharmaceutical Technology July 2006.
[13] ICH, “Validation of Analytical Procedures: Text and Methodology”, Q2(R1), 2005.
[14] J. Ermer and J. H. McB. Miller, “Method Validation in Pharmaceutical Analysis: A Guide to Best Practice,” Wiley, January 2005.
[15] D. M. Bliesner, “Validating Chromatographic Methods: A Practical Guide,” Wiley, 2006.

  
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