Obtaining of the pharmacopoeial reference sample of the mandelic acid isopropyl ester
Keywords:UDC 547.588.11, 54.057, 006.034
In accordance with the requirements of the International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) each monograph for a drug must include the test for related impurities. Impurities in a medicinal product may appear as initial, intermediate or side products of the synthesis and during storage.
Aim. To obtain the impurity of the pregabalin substance – a high-purity isopropyl ester of mandelic acid in order to provide the domestic pharmaceutical market with the pharmacopoeial reference sample of the State Pharmacopoeia of Ukraine (RS SPhU) in the framework of the program for import substitution of reference samples.
Materials and methods. To obtain RS SPhU of the mandelic acid isopropyl ester the traditional methods of organic synthesis, X-ray diffraction analysis, 1H and 13C NMR-spectroscopy, absorption spectrophotometry in the infrared region, thermogravimetry, the capillary method for determining the melting point, thin-layer and liquid chromatography were used, determination of water was performed by K. Fischer titration.
Results and discussion. The simple method for the synthesis of 1-methylethyl-(2RS)-2-hydroxy-2-phenylacetate with mandelic acid and 2-propanol in the presence of catalytic amounts of inorganic acids, as well as its subsequent purification with a final yield of over 90 % have been proposed.
Conclusions. As a result of the study isopropyl ester of mandelic acid has been synthesized, and the effective method of its purification providing a high degree of purity of the target compound has been selected. By its characteristics the substance obtained fully complies with the requirements of the LGC international certificate as a RS and can be used for the qualitative and quantitative determination of a related impurity in the pregabalin substance.
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