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

The synthesis and study of profiles of the ornidazole impurities

Dmytro Leontiev, Olena Bevz, Natalia Volovyk, Ivan Gella, Victoria Georgiyants

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


Keywords


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

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References


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GOST Style Citations


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