ABSTRACT:
A simple, sensitive, and reliable method has been developed for quantitative analysis of an Anti-neoplastic drug Pemetrexed Disodium Hemipentahydrate (PDH) using reversed phase high performance liquid chromatography (RP-HPLC). This method is developed and validated as per the International Council on Harmonisation (ICH) guidelinesQ2(R1). The effective chromatographic separations were achieved on Zorbax SB C8, (4.6 x 150mm) 3.5µ column with isocratic elution programme. The mobile phase is as homogeneous mixture of 0.17% glacial acetate acid with 5.3 pH and acetonitrile in the ratio of 89:11. The delivered flow rate of mobile phase is 2.0 mL/min using UV/PDA detector. The column oven temperature is 30°C and the injection volume is 20.0µL. This method is linear with correlation coefficient being 0.99992 and %Y intercept of 0.16. The repeatability and intermediate precision are evaluated and %RSD for these assays is 0.09 and 0.28, respectively, with overall % RSD of 0.22. Robustness studies do not shows significant change for the system suitability criteria like tailing factor, theoretical plates and %RSD. The values of these criteria are well within acceptance limit. The degradation of Pemetrexed under various stress condition is studied and all known as well as degradants impurities are well separated from the PDH peak. This RP-HPLC method is precise, accurate, and rapid; it also qualifies all the criteria of linearity, stability as well as robustness.
Cite this article:
Vitthal M. Dhalape, Santosh T. Khadangale, Rahul V. Pinjari. RP-HPLC Method Validation for Quantitative Analysis of Pemetrexed Disodium Hemipentahydrate. Research J. Pharm. and Tech. 2020; 13(8):3685-3689. doi: 10.5958/0974-360X.2020.00652.6
Cite(Electronic):
Vitthal M. Dhalape, Santosh T. Khadangale, Rahul V. Pinjari. RP-HPLC Method Validation for Quantitative Analysis of Pemetrexed Disodium Hemipentahydrate. Research J. Pharm. and Tech. 2020; 13(8):3685-3689. doi: 10.5958/0974-360X.2020.00652.6 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2020-13-8-26
REFERENCES:
1. Novak K, Drug Facts and Comparisons, 59th ed.; Wolters Kluwer Health, St. Louis, MO, USA, 2005, p. 2283.
2. Cohen M, Justice R, Pazdur R. Approval summary, Pemetrexed in the initial treatment of advanced/metastatic non-small cell lung cancer, Oncologist 2009, 14(9); p. 930–935.
3. Sweetman S, Antineoplastics and Immune Suppressants, In Martindale, The complete drug reference, 13th ed. The Pharmaceutical Press, London, UK, 2002, p. 564.
4. O’Neil M, The Merck Index, an Encyclopedia of Chemicals, Drugs and Biologicals, 4th ed. Merck Research Laboratories, Whitehouse Station, NJ, USA, 2006, p. 7079.
5. Fukuoka E, Makita M, Nakamura Y. Glassy state of pharmaceuticals, Relaxation during cooling and heating of glass by differential scanning calorimetry, Chemical and Pharmaceutical Bulletin, 1991; 39: p. 2087–2090.
6. Sidoryk K, Malinska M, Bankowski K, Kubiszewski M, Laszcz M, Bodziachowska-Panfil M, Kossykowska M, Giller T, Kutner A, Woźniak K. Physicochemical characteristics of sunitinib malate and its process-related impurities. Journal of Pharmaceutical Sciences, 2013, 102(2);p. 706–716.
7. Pemetrexed disodium heptahydrate, In European Pharmacopoeia, EDQM, Council of Europe, Strasbourg, France, 2013; Volume 8, p. 2637.
8. Chelius E, Reutzel-Edens S, Van den Berghe Snorek S, A Novel Crystalline Form of N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid and Process Therefor. Int. Patent Appl. WO 01/62760 A2, 30 August 2001.
9. Palle R, Nariyam S, Patel V, Vinjamuri R, Devarakonda S, Yarraguntla S, Mudapaka V, Nalivela V, Solid Forms of Pemetrexed. Int. Patent Appl. WO 2008/124485 A2, 16 October 2008.
10. Li J, Cai Z, Wang M, Amorphous Polymorph for Pemetrexed Disodium and Preparation Method Pat. Appl. No.101575338, 11 November 2009.
11. Patel N, Kilaru S, Thennati R. Stable Amorphous Form of Pemextred Disodium. Europ. Pat. Appl. No. 2072518 A1, 24 June 2009.
12. Patel N, Kilaru S, Thennati R. Stable Amorphous Form of Pemetrexed Disodium. US Pat. Appl. No. 2009/181990 A1, 16 July 2009.
13. Kadaboina R, Nariyam S, Ramakrishnan S, Peddireddy S, Baig M, Duggirala N, Amorphous Pemetrexed Disodium. Int. Patent Appl. WO 2010/028105, 11 March 2010.
14. Palle R, Nariyam S, Patel V, Vinjamuri R, Devarakonda S, Yarraguntla S, Mudapaka V, Nalivela V, Solid Forms of Pemetrexed. US Pat. Appl. No. 2010/063072, A1, 11 March 2010.
15. Kadaboina R, Nariyam M, Ramakrishnan S, Peddireddy S, Baig M, Duggirala N. Amorphous Pemetrexed Disodium. Int. Patent Appl. PCT/US2009/055815, 3 SEP. 2009.
16. ICH guidelines, Q8 (R2), Harmonised Tripartite Guideline, on Pharmaceutical development. Proceedings of the International Conference on Harmonization, 2009.
17. ICH guidelines, Q3A(R2), Impurities in new drug substances, in: International Conference on Harmonization, Geneva, 2006.
18. ICH guidelines, Q1A(R2), Stability Testing of New Drug Substances and Products, International Council on Harmonization Geneva, 2003.
19. ICH guidelines, Q2(R1), Validation of Analytical Procedures, Text and Methodology, International Conference on Harmonization Geneva.
20. Ngwa G, Forced degradation as an integral part of HPLC stability-indicating method development. Drug Delivery Technology, 2010;10(5); p.56-9.
21. Blessy M, Patel R, Prajapati P, Agrawal Y. Development of forced degradation and stability, indicating studies of drugs-a review. Journal of Pharmaceutical Analysis, 2014;4(3); p.159-65.