Development and Validation of an Ion Chromatography Method for Quantification of Ammonium Ions in STEALTH® Liposomes

Document Type: Research Paper

Authors

1 Department of Chemistry, Faculty of Science, University of Guilan, Namjoo Street, P.O. Box 1914, Rasht, Iran

2 Department of Chemistry, Pardis Campus, University of Guilan, Park-e-Shahr, Rasht, Iran

3 Sobhan Oncology Co. No. 11, 5th Alley, Bucharest Ave., Argentina Sq, Tehran, Iran

Abstract

Ammonium sulfate is one of the subsidiary components in the stealth liposome structure. The ratio of ammonium ion bound to liposome sphere to ammonium ions outside the liposome plays an important role in drug delivery formulation; accordingly, in order to quantify the ammonium ion in the liposome structure, a rapid and sensitive method was validated using a conductivity detector. Through this method, the amount of ammonium enclosed in the liposomal spheres is determined by subtracting the amount of extra-liposomal ammonium content from the total amount of ammonium present in the liposome structure. Destruction of the liposome structure with the aid of 1% w/w Triton-X-100 solution allows for the analysis of the total ammonium ion present in the liposome structure. In the present research, ultrafiltration made it possible to isolate and analyze the extra-liposomal ammonium ions. This measurement was performed using an ion exchange chromatography column, isocratic elution flow and a linearity of 0.9998. Based on this signal-to-noise method, LOD was determined as 0.0003 mmol/L ammonium ion, with a signal-to-noise ratio of 3:1 and RSD was 1.4%. With a signal-to-noise ratio of 10:1, LOQ was determined as 0.001 mmol/L ammonium ion with RSD 1.2%. In the determination of the total ammonium ion, the individual percentage recovery ranged from 100.00 to 100.93% and for the external ammonium ion analysis, the individual percentage recovery varied from 95.87 to 98.12% for all three levels and RSDs are 0.27, 0.71, and 0.71% for these concentrations.

Keywords


[1]       S. Deepu, M. Mathew, M.S. Shamna, Int. J. Pharm. Chem. Sci. 3 (2014) 636.

[2]       B. Jeong, S.W. Kim, Y.H. Bae, Adv. Drug Deliv. Rev. 54 (2002) 37.

[3]       A.D. Bangham, M.M. Standish, J.C. Watkins, J. Mol. Biol. 13 (1965) 238.

[4]       V. Torchilin, V. Weissig (Eds.), Liposomes: a practical approach, Oxford University Press, 2003.

[5]       F.M. Veronese, M. Harris, Adv. Drug Deliv. Rev. 54 (2002) 453.

[6]       A.D. Bangham, Annu Rev. Biochem. 41 (1972) 753.

[7]       G. Sessa, G. Weissmann, J. Lipid Res. 9 (1968) 310.

 

 

[8]       A. Akbarzadeh, R. Rezaei-Sadabady, S. Davaran, S.W. Joo, N. Zarghami, Y. Hanifehpour, M. Samiei, M. Kouhi, K. Nejati-Koshki, Nanoscale Res. Lett. 8 (2013) 102.

[9]       H. Pandey, R. Rani, V. Agarwal, Braz. Arch. Biol. Technol. 59 (2016) 1.

[10]    J. Li, X. Wang, T. Zhang, C. Wang, Z. Huang, X. Luo, Y. Deng, Asian J. Pharm. Sci. 10 (2015) 81.

[11]    A. Laouini, C. Jaafar-Maalej, I. Limayem-Blouza, S. Sfar, C. Charcosset, H. Fessi, J. Colloid Sci. Biotechnol. 1 (2012) 147.

[12]    N. Tyagi, S.S. Rathore, P.C. Ghosh, Drug Deliv. 18 (2011) 394.

[13]    D.D. Lasic, P.M. Frederik, M.C. Stuart, Y. Barenholz, T.J. McIntosh, FEBS Lett. 312 (1992) 255.

[14]    U. Bulbake, S. Doppalapudi, N. Kommineni, W. Khan, Pharmaceutics 9 (2017) 1.

[15]    C. Allen, N. Dos Santos, R. Gallagher, G.N. Chiu, Y. Shu, W.M. Li, S.A. Johnstone, A.S. Janoff, L.D. Mayer, M.S. Webb, M.B. Bally, Biosci. Rep. 22 (2002) 225.

[16]    A. Gabizon, R. Catane, B. Uziely, B. Kaufman, T. Safra,  R.  Cohen, F.  Martin, A. Huang, Y. Barenholz,

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

             

   
   

Development and Validation of an Ion Chromatography     Method/Anal. Bioanal. Chem. Res.,Vol. 7, No. 1, 17-31, June 2020.

   

 

   
   
 

 

 

 

Cancer Res. 54 (1994) 987.

[17]    R.C. Leonard, S. Williams, A. Tulpule, A.M. Levine, S. Oliveros, The Breast18 (2009) 218.

[18]    P.K. Working, A.D. Dayan, Hum. Exp. Toxicol. 15 (1996) 751.

[19]    M.L. Immordino, F. Dosio, L. Cattel, J. Nanomedicine 1 (2006) 297.

[20]    D.D. Lasic, N. Needham, Chem. Rev. 95 (1995) 2601.

[21]    P. Tardi, N. Boman, P. Cullis, J. Drug Target. 4 (1996) 129.

[22]    W.C. Zamboni, Clin. Cancer Res. 11 (2005) 8230.

[23]    D.D. Lasic, F.J. Martin, Stealth Liposomes, CRC Press, 1995.

[24]    T. Ishida, M.J. Kirchmeier, E.H. Moase, S. Zalipsky, T.M. Allen, Biochim. Biophys. Acta 1515 (2001) 144.

[25]    ICH Harmonized Tripartite Guideline Q2B: Validation of Analytical Procedures: Methodology, 1996.

[26]    United State Pharmacopeia 39, United State Pharmacopeial Convention, 2015.

[27]    S.H. Wang, E. Raptis, J. Yeh, J. Chromatogr. A 1039 (2004) 51.