Article metrics

  • citations in SCindeks: [1]
  • citations in Google Scholar:[=>]
  • visits in previous 30 days:2
  • full-text downloads in 30 days:0
article: 1 from 1  
Arhiv za farmaciju
2012, vol. 62, iss. 5, pp. 475-488
article language: Serbian
Professional Paper

Robustness testing of liquid chromatographic method for determination of itraconazole and its impurities applying fractional factorial design
aUniverzitet u Banjoj Luci - Medicinski fakultet, Katedra za analitiku lijekova, Banja Luka, Republika Srpska, BiH
bUniverzitet u Beogradu, Farmaceutski fakultet, Institut za farmaceutsku hemiju i analitiku lekova



Modelling of different chromatographic systems with chemometrical approach in pharmaceutical analysis (MESTD - 172052)


Test of robustness is a part of the method validation and it is carried out in the end of the method development or in the beginning of the method validation. The purpose of robustness testing is to avoid problems in interlaboratory studies and to define parameters with the greatest impact on the method. The chosen factors are investigated within the range that slightly exceeds the expected variations when the method is transferred from one instrument/laboratory to another. The application of experimental design is recommended to perform robustness testing and two most often utilized - Plackett-Burman and fractional factorial design - are described. Furthermore, the manners of evaluation of factor significance, the methods for calculation of the range of insignificance for significant factors and the procedure for determination of system suitability test parameters are described. Such an approach of robustness testing was applied to the high performance liquid chromatographic method for determination of itraconazole and its impurities B and F. The robustness is tested by using fractional factorial design and 4 factors in 11 experiments were analyzed. After the application and the analysis of all the suggested steps for robustness, the impact of factors on the system responses was evaluated, insignificance ranges were defined and system suitability test limits for suggested method were determined.



*** (1994) Harmonised Tripartite Guidline. in: Third International Conference on Harmonisation of Technical Requirmants for the Registration of Pharmaceuticals for Human Use (ICH), Text on Validation of Analytical Procedures, London
*** (2011) European Pharmacopoeia 7.0. Strasbourg, France: European Directorate for the Quality of Medicines & HealthCare (EDQM) - Council of Europe, Vol 1. 01
Chen, W., Gu, B., Wang, H., Pan, J., Lu, W., Hou, H. (2008) Development and evaluation of novel itraconazole-loaded intravenous nanoparticles. International Journal of Pharmaceutics, 362(1-2): 133-140
Dejaegher, B., Dumarey, M., Capron, X., Bloomfield, M.S., Vander, H.Y. (2007) Comparison of Plackett-Burman and supersaturated designs in robustness testing. Analytica chimica acta, 595(1-2): 59-71
Dumarey, M., Sneyers, R., Janssens, W., Somers, I., Vander, H.Y. (2009) Drug impurity profiling: Method optimization on dissimilar chromatographic systems: Part I: pH optimization of the aqueous phase. Analytica chimica acta, 656(1-2): 85-92
Ekiert, R.J., Krzek, J., Talik, P. (2010) Chromatographic and electrophoretic techniques used in the analysis of triazole antifungal agents-a review. Talanta, 82(4): 1090-100
Gagliardi, L., de Orsi, D., Chimenti, P., Porra', R., Tonelli, D. (2003) HPLC determination of imidazole antimycotis in antidandruff cosmetic products. Analytical sciences, 19(8): 1195-7
Koks, C.H., Sparidans, R.W., Lucassen, G., Crommentuyn, K.M., Beijnen, J.H. (2002) Selective high-performance liquid chromatographic assay for itraconazole and hydroxyitraconazole in plasma from human immunodeficiency virus-infected patients. Journal of Chromatography B, 767(1): 103-110
Lundstedt, T., Seifert, E., Abramo, L., Thelin, B., Nyström, Å., Pettersen, J., Bergman, R. (1998) Experimental design and optimization. Chemometrics and Intelligent Laboratory Systems, 42(1-2): 3-40
Mašković, M., Jančić-Stojanović, B., Malenović, A., Ivanović, D., Medenica, M. (2010) Assessment of liquid chromatographic method robustness by use of Plackett-Burman design. Acta Chromatographica, 22(2): 281-296
Parikh, S.K., Patel, A.D., Dave, J.B., Patel, C.N., Sen, D.J. (2011) Development and validation of UV spectrophotometric method for estimation of itraconazole bulk drug and pharmaceutical formulation. International Journal of Drug Development & Research, 3(2), 324-328
Srivatsan, V., Dasgupta, A.K., Kale, P., Datla, R.R., Soni, D., Patel, M., Patel, R., Mavadhiya, C. (2004) Simultaneous determination of itraconazole and hydroxyitraconazole in human plasma by high-performance liquid chromatography. Journal of chromatography. A, 1031(1-2): 307-13
Vander, H.Y., Nijhuis, A., Smeyers-Verbeke, J., Vandeginste, B.G., Massart, D.L. (2001) Guidance for robustness/ruggedness tests in method validation. Journal of pharmaceutical and biomedical analysis, 24(5-6): 723-53
Vander, H.Y., Jimidar, M., Hund, E., Niemeijer, N., Peeters, R., Smeyers-Verbeke, J., Massart, D.L., Hoogmartens, J. (1999) Determination of system suitability limits with a robustness test. Journal of Chromatography A, 845(1-2): 145-154
Wong, J.W., Nisar, U., Yuen, K.H. (2003) Liquid chromatographic method for the determination of plasma itraconazole and its hydroxy metabolite in pharmacokinetic/bioavailability studies. Journal of Chromatography B, 798(2): 355-360