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Ultra-High Performance Method on Superficially Porous Stationary Phase for the Determination of Related Substances in Pitavastatin Calcium by HPLC

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Abstract

A simple reverse-phase method for the selective quantification of pitavastatin calcium (PIT) and its related substances was developed. The method demonstrated an excellent separation between PIT and each of 15 impurities (including its isomers and degradants) within a short run time of 12 min by HPLC. A rapid resolution similar to that of UHPLC was achieved using high flow rate on superficially porous C18 stationary phase. A synergistic combination of quality by design approach and use of a superficially porous column delivered a HPLC method with ultra-high performance. Forced degradation studies proved the method to be highly specific (mass balance > 98 %) and the structures of major degradation products were proposed based on LC–MS analysis. The results of validation proved the method to be highly precise (%RSD < 4), accurate (recoveries in range of 100 ± 7 %), linear (r 2 > 0.999) and sensitive (LOQ ≤ 0.02 % and LOD ≤ 0.005 %) for all the impurities and drug. Use of multivariate analysis helped to incorporate high robustness in the method. The method is valuable for quantification of PIT and its related substances in both drug substance and oral solid dosage form.

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Acknowledgments

The authors wish to thank Dr. S. Rajeswar, Management of Dr. Reddy’s Laboratories and Jawaharlal Nehru Technological University for supporting this work.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Integrated Product Development Organization, Dr. Reddy’s Laboratories Ltd., Bachupally, Hyderabad, 500072, India

    B. Hariram, R. Suresh Kumar, Dama Venugopala Rao, L. Kalyanaraman & Katkam Srinivas

  2. Centre for Chemical Sciences and Technology, Jawaharlal Nehru Technological University-Hyderabad, Kukatpally, Hyderabad, 500085, India

    B. Hariram & Anireddy Jaya Shree

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  1. B. Hariram
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  2. R. Suresh Kumar
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  3. Anireddy Jaya Shree
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  4. Dama Venugopala Rao
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  5. L. Kalyanaraman
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  6. Katkam Srinivas
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Correspondence to B. Hariram.

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Hariram, B., Kumar, R.S., Jaya Shree, A. et al. Ultra-High Performance Method on Superficially Porous Stationary Phase for the Determination of Related Substances in Pitavastatin Calcium by HPLC. Chromatographia 78, 1017–1029 (2015). https://doi.org/10.1007/s10337-015-2922-y

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  • DOI: https://doi.org/10.1007/s10337-015-2922-y

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