Features of the development of pharmaceutical substances reference materials

This article considers the features of developing pharmaceutical substances reference materials using the example of thiamine hydrochloride. It describes the developing procedure for reference materials: preliminary authentication of main substance of a certified pharmaceutical substance, determination of the mass fraction of main substance by direct (titrimetry) and indirect (mass balance) methods, verification of the feasibility of methods for assessing all impurities, provision of the traceability of certified value. The results of infrared Fourier spectrometry confirm the authenticity of the analyzed substance of thiamine hydrochloride. The measurements of mass fraction of main substance was carried out using acid-base titration in aqueous-alcoholic medium, as well as mass balance method, taking into account the content of sulfate ash, water, related impurities, and residual organic solvents. The expanded uncertainty of measurement results of the mass fraction of main substance and groups of impurities was evaluated by constructing a full uncertainty budget. It has been established that the measurements results of the mass fraction of main substance in the substance of thiamine hydrochloride, obtained by a titrimetric method (97.36±0.40) % and a mass balance method (97.37±0.08) %, are consistent with each other within the stated uncertainties. The metrological traceability of the certified value of reference material to the units of quantities reproduced by state primary measurement standards (State primary measurement standard for unit of mass GET 3-2020, State primary measurement standard for units of mass fraction and mass (molar) concentration of water in liquid and firm substances and materials GET 173-2017, State primary measurement standard for units of mass (molar, atomic) fraction and mass (molar) concentration of components in liquid and solid substances and materials based on coulometry GET 176-2019, State primary measurement standard for units of mass (molar) fraction and mass (molar) concentration of organic components in liquid and solid substances and materials based on liquid and gas chromatography-mass spectrometry with isotope dilution and gravimetry GET 208-2019) was ensured. The results are relevant for ensuring the uniformity of measurements in the quality control of medicines.

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