Issue

Vol. 32 No. 2 (2020): Vol 32 Issue 2

Copyright (c) 2020 AJC

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Design of Experimental Approach to Analytical Robustness Study for UHPLC Method Developed for Separation and Quantification of Spironolactone and its Impurities in Drug Substances

https://doi.org/10.14233/ajchem.2020.22224
Y.V.S. Veerendra
Electroanalytical Lab, Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram-522502, India; USP-India Private Limited, Hyderabad-500101, India
Pradeep Kumar Brahman
Electroanalytical Lab, Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram-522502, India
Sharad D. Mankumare
USP-India Private Limited, Hyderabad-500101, India
Jaya Raju CH
USP-India Private Limited, Hyderabad-500101, India
J. Satish
USP-India Private Limited, Hyderabad-500101, India

Corresponding Author(s) : Pradeep Kumar Brahman

veerendrayvs@gmail.com

Asian Journal of Chemistry, Vol. 32 No. 2 (2020): Vol 32 Issue 2

Abstract

The present work demonstrates the development of an optimal, robust, validated UHPLC method for quantification of related impurities and assay determination of spironolactone. Design of experiment procedure, in combination with statistical evaluation of the data was used to test the robustness of developed method. A stability indicating method was established by forced degradation experiments. Analytical robustness was determined using design of experiment approach. The chromatographic separation was achieved with Agilent SB-C18 RRHD column using gradient elution with mobile phase-A consists of a mixture of 0.1 % each formic acid and ammonia in water and methanol as mobile phase-B respectively. The developed method is exhaustively validated for parameters like precision, accuracy, linearity, LOD, LOQ, ruggedness and robustness. The stability tests were also performed on drug substances as per ICH norms. Base line separation was achieved for all impurities, degradation products and the API. All impurities were eluted within 12 min, there was a remarkable 3.5-fold decrease in runtime and a clear baseline separation between all peaks in comparison with Ph.Eur monograph. A multi-dimensional design space was built to study the robustness of developed method using design expert software. Significant parameters such as effect of flow rate, buffer strength and mobile phase compositions were optimized at three levels. Plackett-Burman design was applied for screening of chromatographic conditions and factorial design was applied for optimization of essential factors in robustness studies.

Keywords

Spironolactone Design of experiments UHPLC Stability indicating method Robustness Plackett-Burman design
Veerendra, Y., Brahman, P. K., Mankumare, S. D., CH, J. R., & Satish, J. (2019). Design of Experimental Approach to Analytical Robustness Study for UHPLC Method Developed for Separation and Quantification of Spironolactone and its Impurities in Drug Substances. Asian Journal of Chemistry, 32(2), 219–227. https://doi.org/10.14233/ajchem.2020.22224
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. 19th WHO Model List of Essential Medicines, April (2015).
  2. United States Pharmacopoeia, Validation of Compendial Procedures, edn 40 (2017).
  3. Pharmaceutical Development Q8 (R2), ICH Harmonized Pripartite Guidelines, Geneva (2009).
  4. K. Monks, I. Molnar, H.J. Rieger, B. Bogati and E. Szabo, J. Chromatogr.A, 1232, 218 (2012); https://doi.org/10.1016/j.chroma.2011.12.041.
  5. R. Kormαny, J. Fekete, D. Guillarme and S. Fekete, J. Pharm. Biomed. Anal., 89, 67 (2014); https://doi.org/10.1016/j.jpba.2013.10.029.
  6. Y. Vander Heyden, A. Nijhuis, J. Smeyers-Verbeke, B.G.M. Vandeginste and D.L. Massart, J. Pharm. Biomed. Anal., 24, 723 (2001); https://doi.org/10.1016/S0731-7085(00)00529-X.
  7. L. Vlase, S. Imre, D. Muntean, M. Achim and D.-L. Muntean, Croat. Chem. Acta, 84, 361 (2011); https://doi.org/10.5562/cca1761.
  8. M.A. Hegazy, F.H. Metwaly, M. Abdelkawy and N.S. Abdelwahab, J. Chromatogr. Sci., 49, 129 (2011); https://doi.org/10.1093/chrsci/49.2.129.
  9. M.I. Walash, N. El-Enany, M.I. Eid and M.E. Fathy, Anal. Methods, 5, 5644 (2013); https://doi.org/10.1039/c3ay41110a.
  10. H. Dong, F. Xu, Z. Zhang, Y. Tian and Y. Chen, J. Mass Spectrom., 41, 477 (2006); https://doi.org/10.1002/jms.1006.
  11. D.I. Sora, S. Udrescu, F. Albu, V. David and A. Medvedovici, J. Pharm.Biomed. Anal., 52, 734 (2010); https://doi.org/10.1016/j.jpba.2010.03.004.
  12. V. Subramanian, K. Nagappan and S.S. Mannemala, Acta Chim. Slov., 62, 633 (2015); https://doi.org/10.17344/acsi.2014.1262.
  13. P. Prajapati, C. Chandarana, V. Modi and T. Basuri, Int. J. Pharm. Chem. Anal., 3, 168 (2016); https://doi.org/10.5958/2394-2797.2016.00024.1.
  14. S.S. Israt, M.N. Uddin, R.A. Jahan and M.M. Karim, Bangladesh J. Sci. Ind. Res., 51, 297 (2016); https://doi.org/10.3329/bjsir.v51i4.30450.
  15. V.R. Ram, P.N. Dave and H.S. Joshi, J. Chromatogr. Sci., 50, 721 (2012); https://doi.org/10.1093/chromsci/bms062.
  16. I.C.H. Harmonised Tripartite Guidline, Stability Testing of New Drug Substances and Products Q1A(R2), in Proceedings of the International Conference on Harmonization (IFPMA’03), Geneva, Switzerland, Current Step 4 version dated 6 February (2003).
  17. United States Pharmacopoeia, United States Pharmacopeial Convention, Rockville, USA, edn 40 (2017).
  18. T.C. Jens and C.T. Rhodes, Drug Stability Principles and Practices, Marcel Dekker: New York, NY, USA, edn 3 (2000).
  19. M. Bakshi and S. Singh, J. Pharm. Biomed. Anal., 28, 1011 (2002); https://doi.org/10.1016/S0731-7085(02)00047-X.
  20. H. Hashem, A.E. Ibrahim and M. Elhenawee, J. Sep. Sci., 37, 2814 (2014); https://doi.org/10.1002/jssc.201400276.
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 0 Download : 0