The synthesis and study of profiles of the ornidazole impurities

Authors

  • Dmytro Leontiev Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085 National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002, Ukraine https://orcid.org/0000-0003-1129-8749
  • Olena Bevz National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002 Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085, Ukraine https://orcid.org/0000-0002-7695-3612
  • Natalia Volovyk Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085, Ukraine https://orcid.org/0000-0002-9660-8162
  • Ivan Gella V. N. Karazin Kharkiv National University Svobody sq., 4, Kharkiv, Ukraine, 61022 Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085, Ukraine https://orcid.org/0000-0003-4069-2411
  • Victoria Georgiyants National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002, Ukraine https://orcid.org/0000-0001-8794-8010

DOI:

https://doi.org/10.15587/2519-4852.2018.123387

Keywords:

ornidazole impurities, synthesis, ornidazole-diol, ornidazole-epoxide, profile of impurities, ornidazole substance, infusion solution of ornidazole, pharmacopoeial reference standards, State Pharmacopeia of Ukraine

Abstract

Pharmacopoeial reference standards (PhRSs) provide the comparability of the test results of generic drugs. PhRSs of ornidazole impurities are not described in pharmacopoeias. Therefore, the establishment of PhRSs of the State Pharmacopeia of Ukraine (SPhU RSs) of ornidazole impurities is an essential task, the integral part of which is synthesis and characterisation of ornidazole impurities.

Aim: To synthesise impurities of ornidazole as candidate materials for certification as SPhU RSs and study their profiles in the substance and infusion solution of ornidazole.

Methods: Traditional methods of organic synthesis, 1Н NMR spectroscopy, IR absorption spectrophotometry, the capillary method for the melting point determination, liquid chromatography with a spectrophotometric detector.

Results: Ornidazole-diol and ornidazole-epoxide were synthesized, and their structures were confirmed using 1Н NMR and IR spectra. Their chromatographic profiles in the substance and the infusion drug of ornidazole being under pharmaceutical development were studied. The problem with the ornidazole-diol determination by the manufacturer’s procedure was found, and its correction was proposed. The purity of the compounds synthesized was approximately 99.5 %. In the substance, the content of ornidazole-epoxide exceeded 0.1 %, whereas the content of ornidazole-diol was negligible. In the drug, the content of ornidazole-epoxide reduced to zero with time, while the content of ornidazole-diol increased considerably (to approx. 3 %).

Conclusions: The efficient methods for the synthesis of ornidazole-epoxide and ornidazole-diol were developed, and the synthesis was conducted. The profiles of the synthesized impurities in the substance and the infusion drug of ornidazole being under pharmaceutical development were studied. It was found that ornidazole-epoxide and ornidazole-diol are present in the substance and the drug at the level which requires their identification and quantitative determination. The proposed methods for synthesis provide obtaining ornidazole-diol and ornidazole-epoxide of high purity, which enables to use them as the candidate materials for certification as SPhU RSs

Author Biographies

Dmytro Leontiev, Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085 National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of Pharmaceutical Sciences, Senior Researcher, Head of Department

Department of Validation and Reference Standards

Professor

Department of Pharmaceutical Chemistry

Olena Bevz, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002 Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085

Postgraduate student

Department of Pharmaceutical Chemistry

Junior Researcher

Department of Validation and Reference Standards

Natalia Volovyk, Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085

PhD

Department of Validation and Reference Standards

Ivan Gella, V. N. Karazin Kharkiv National University Svobody sq., 4, Kharkiv, Ukraine, 61022 Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines Astronomichna str., 33, Kharkiv, Ukraine, 61085

PhD, Senior Researcher

Department of Organic Chemistry

Senior Researcher

Department of Validation and Reference Standards

Victoria Georgiyants, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of Pharmaceutical Sciences, Professor, Head of Department

Department of Pharmaceutical Chemistry

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Published

2018-02-12

How to Cite

Leontiev, D., Bevz, O., Volovyk, N., Gella, I., & Georgiyants, V. (2018). The synthesis and study of profiles of the ornidazole impurities. ScienceRise: Pharmaceutical Science, (1 (11), 4–11. https://doi.org/10.15587/2519-4852.2018.123387

Issue

No. 1 (11) (2018)

Section

Pharmaceutical Science

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Copyright (c) 2018 Dmytro Leontiev, Olena Bevz, Natalia Volovyk, Ivan Gella, Victoria Georgiyants

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