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Vol. 29 No. 8 (2017): Vol 29 Issue 8

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An Orthogonal Approach for Method development, Validation and Trace Level Quantification of 2,5-Diamino-4,6-dichloro Pyrimidine Impurity in Abacavir Sulfate by LC-MS/MS and GC-MS

https://doi.org/10.14233/ajchem.2017.20679
Nagaraju Rajana
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy’s Laboratories Ltd., Miyapur, Hyderabad-500 049, India; Department of Inorganic & Analytical Chemistry, Andhra University, Visakhapatnam-530 003, India
P. Madhavan
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy’s Laboratories Ltd., Miyapur, Hyderabad-500 049, India
H. Rama Mohan
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy’s Laboratories Ltd., Miyapur, Hyderabad-500 049, India
J. Moses Babu
Integrated Product Development Organization, Dr. Reddy’s Laboratories Ltd, Innovation Plaza, Bachupally, Hyderabad-500 072, India
K. Basavaiah
Department of Inorganic & Analytical Chemistry, Andhra University, Visakhapatnam-530 003, India

Corresponding Author(s) : Nagaraju Rajana

nagarajurajana@drreddys.com; nagarajrajana@gmail.com

Asian Journal of Chemistry, Vol. 29 No. 8 (2017): Vol 29 Issue 8

Abstract

The trace level quantification of 2,5-diamino-4,6-dichloro pyrimidine (DADCP) present in abacavir sulfate by LC-MS/MS and GC-MS has been proposed. LC-MS/MS method was established for 2.5 ppm with respect to test concentration (10 mg/mL), LOQ and LOD were established as 1.3 and 0.4 ppm, respectively. Linearity, method precision, accuracy at LOQ, 100 %, 150 %, solution, mobile phase stability and robustness parameters were studied against the ICH Q2(R1) guideline. Similarly, the GC-MS method was established for 2.5 ppm of 2,5-diamino-4,6-dichloro pyrimidine with respect to test concentration (50 mg/mL), LOQ and LOD were established as 1.1 and 0.4 ppm, respectively. Linearity, method precision, accuracy at LOQ, 100 %, 150 %, solution stability and robustness parameters were studied against the ICH Q2 (R1). No analytical method was found in trace level quantification of 2,5-diamino-4,6-dichloro pyrimidine in abacavir sulfate. The orthogonal method of LC-MS/MS and GC-MS was well robust and can be used for determination of trace level of 2,5-diamino-4,6-dichloro pyrimidine in different pharmaceutical compounds.

Keywords

Quantification 2,5-Diamino-4,6-dichloro pyrimidine Abacavir sulfate LC-MS/MS GC-MS
Rajana, N., Madhavan, P., Mohan, H. R., Babu, J. M., & Basavaiah, K. (2017). An Orthogonal Approach for Method development, Validation and Trace Level Quantification of 2,5-Diamino-4,6-dichloro Pyrimidine Impurity in Abacavir Sulfate by LC-MS/MS and GC-MS. Asian Journal of Chemistry, 29(8), 1853–1858. https://doi.org/10.14233/ajchem.2017.20679
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References
  1. Abacavir Sulfate, The American Society of Health-System Pharmacists, Retrieved 31 July 2015.
  2. http://www.drugbank.ca/drugs/DB01048.
  3. G. Moyle, M. Boffito, C. Fletcher, C. Higgs, P.E. Hay, I.H. Song, Y. Lou, G.J. Yuen, S.S. Min and E.M. Guerini, Antimicrob. Agents Chemother., 53, 1532 (2009); https://doi.org/10.1128/AAC.01000-08.
  4. J.R. Huff, Bioorg. Med. Chem., 7, 2667 (1999); https://doi.org/10.1016/S0968-0896(99)00242-4.
  5. P. Vukkum, G.R. Deshpande, J.M. Babu, R. Muralikrishna and P. Jagu, Sci. Pharm., 80, 903 (2012); https://doi.org/10.3797/scipharm.1206-11.
  6. Pavani Jagu, P. Vukkum1, B.M. Rao and N.S. Rao, Int. J. Pharm. Life Sci., 4, 3043 (2013).
  7. M.S. Goizman, T.D. Balayants, G.B. Tikhomirova and N.N. Sal’nikova, Pharm. Chem. J., 46, 187 (2012); https://doi.org/10.1007/s11094-012-0757-5.
  8. C.P.W.G.M. Verweij-van Wissen, R.E. Aarnoutse and D.M. Burger, J. Chromatogr. A, 816, 121 (2005); https://doi.org/10.1016/j.jchromb.2004.11.01.
  9. A.I. Veldkamp, R.W. Sparidans, R.M.W. Hoetelmans and J.H. Beijnen, J. Chromatogr. B Biomed. Sci. Appl., 736, 123 (1999); https://doi.org/10.1016/S0378-4347(99)00457-0.
  10. U. Seshachalam, B. Haribabu and K.B. Chandrasekhar, J. Sep. Sci., 30, 28 (2007); https://doi.org/10.1002/jssc.200600209.
  11. Y. Ozkan, A. Savaser and S.A. Ozkan, J. Liq. Chromatogr. Rel. Technol., 28, 423 (2005); https://doi.org/10.1081/JLC-200044523.
  12. S.M. Ferrer, P. Modamio, C.F. Lastra and E.L. Mariño, Biomed. Chromatogr., 18, 862 (2004); https://doi.org/10.1002/bmc.406.
  13. C.P.W.G.M. Verweij-van Wissen, R.E. Aarnoutse and D.M. Burger, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 816, 121 (2005); https://doi.org/10.1016/j.jchromb.2004.11.019.
  14. T. Tol, N. Kadam, N. Raotole, A. Desai and G. Samanta, J. Chromatogr. A, 1432, 26 (2016); https://doi.org/10.1016/j.chroma.2015.12.080.
  15. B. Dogan, B. Uslu, S.A. Ozkan and P. Zuman, Anal. Chem., 80, 209 (2008); https://doi.org/10.1021/ac0713151.
  16. S.A.B. Shah, R. Mullin, G. Jones, I. Shah, J. Barker, A. Petroczi and D.P. Naughton, J. Pharm. Biomed. Anal., 74, 308 (2013); https://doi.org/10.1016/j.jpba.2012.10.023.
  17. R.N. Rao, R.M. Vali, B. Ramachandra and S.S. Raju, J. Pharm. Biomed. Anal., 54, 279 (2011); https://doi.org/10.1016/j.jpba.2010.08.021.
  18. J.M. Rice and G.O. Dudek, J. Am. Chem. Soc., 89, 2719 (1967); https://doi.org/10.1021/ja00987a039.
  19. ICH Q1A(R2), Stability Testing of New Drug Substances and Products, (2000).
  20. ICH Q3A(R2), Current Step 4 Version, Impurities in New Drug Substances, October (2006).
  21. ICH Q2(R1), Validation of Analytical Procedures: Text and Methodology, November (2005).
  22. M7(R1) ICH Consensus Guideline, Released for Consultation on 9 June (2015).
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