Validation of the method for determination of related impurities in the active antiviral ingredient of enisamium iodide

Authors

  • O. V. Burmaka Central Laboratory of Pharmaceutical Development, Farmak JSC, Kyiv, Ukraine,
  • S. M. Hureieva Central Laboratory of Pharmaceutical Development, Farmak JSC, Kyiv, Ukraine,
  • V. M. Marhitych Farmak JSC, Kyiv, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2018.5.141718

Keywords:

enisamium iodide, active pharmaceutical ingredient, related impurities, HPLC, validation studies

Abstract

The aim of the work. To validate a method for the related impurities determination in the enisamium iodide active pharmaceutical ingredient (API) by means of high-performance liquid chromatography (HPLC). To characterize the sensitivity of the method by establishing the limit of detection and limit of quantification for the following impurities: benzylamine, isonicotinic acid (raw materials for API synthesis), isonicotinic acid benzylamide (intermediate product of API synthesis) and unidentified impurities. To confirm the method compatibility with validation characteristics as recommended by the International Conference on Harmonization of Technical Requirements for the Registration of Medicinal Products for Human Use (ICH).

Materials and methods. The liquid chromatograph Agilent 1200 equipped with degasser, four-channel pump, auto sampler, chromatographic column thermostat and diode array detector was used. The Zorbax Eclipse XDB-C18 chromatographic column with dimensions 150.0 ×4.6 mm filled by octadecylsilane sorbent with a particles size of 5 μm, was used. The mobile phase was a mixture of a buffer solution pH 2.5 containing sodium octane-1-sulfonate in an amount of 0.1 %: water : acetonitrile (30 : 44 : 26 v/v/v).

The primary standards of Farmak JSC were used: enisamium iodide (b. 07-16) and isonicotinic acid benzylamide (b. 10413). Other materials and reagents were used with sufficient purity (Sigma-Aldrich).

Results. Detection limits and limits of quantification for identified and unidentified impurities have been determined. Validation characteristics such as specificity, accuracy, precision, range of use, robustness, intermediate precision have been confirmed. The linearity has been confirmed within the range of 0.01–0.06 % for each of the impurities (with a maximum permitted content of each impurity of 0.05 %). The correlation coefficients of linear regression (r) between the entered and found values for each of the determined impurities are greater than 0.990 and the relative confidence intervals (Dz) are at the level not more than 5.0 %. Stability of the test solution, reference solution and solution for system suitability test upon storage at room temperature for 48 hours have been confirmed.

Conclusions. It has been experimentally proved that the described method can be used for quality control of enisamium iodide substance.

References

European Centre for Disease Prevention and Control. Annual epidemiological report 2014 – respiratory tract infections. Stockholm: ECDC. Retrieved from: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/Respiratory-tract-infections-annual-epidemiological-report-2014.pdf.

Boltz, D., Peng, X., Muzzio, M., Dash, P., Thomas, P., Mehta, R., & Margitich, V. (2014) Antiviral activity of enisamium against influenza viruses in differentiated normal human bronchial epithelial cells. Proceedings of the 3rd Antivirals Congress, (P. 46). Amsterdam.

Boltz, D., Cocking, D., Cinatl, J., Peng, X., Jonson, W., Muzzio, M., et al. (2017) Antiviral Effect of a Derivative of Isonicotinic Acid Enisamium Iodide (FAV00A) Against Influenza Virus. Proceedings of the 5th ISIRV AVG Conference. (P. 56). Shanghai.

Burmaka, А. V., Gureeva, S. N., & Margitich, V. M. (2017). Razrabotka metodiki kontrolya soputstvuyushchikh primesej substancii e'nisamiuma yodida [Development of HPLC method for the determination of related substances in API enisamium iodide]. Farmakom, 3, 17–25. [in Russian].

ICH Expert Working Group. (1995). Validation of analytical procedures: text and methodology. London.

Derzhavne pіdpryiemstvo «Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv» (2015). Derzhavna Farmakopeia Ukrainy [State Pharmacopoeia of Ukraine]. (Vol. 1). (P. 891–893). Kharkіv. [in Ukrainian].

Derzhavne pіdpryiemstvo «Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv» (2015). Derzhavna Farmakopeia Ukrainy [State Pharmacopoeia of Ukraine]. (Vol. 1). (P. 924–925). Kharkіv. [in Ukrainian].

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How to Cite

1.
Burmaka OV, Hureieva SM, Marhitych VM. Validation of the method for determination of related impurities in the active antiviral ingredient of enisamium iodide. Zaporozhye medical journal [Internet]. 2018Sep.24 [cited 2024Apr.20];(5). Available from: http://zmj.zsmu.edu.ua/article/view/141718

Issue

No. 5 (2018)

Section

Basic research

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