Features of the Development of Reference Materials of Pharmaceutical Substances

The article considers the features of developing reference materials of pharmaceutical substances using the example of thiamine hydrochloride. It describes the procedure for developing a reference material, which includes preliminary authentication of the main substance of a certified pharmaceutical substance, determination of mass fraction of the main substance by direct (titrimetry) and indirect (mass balance) methods, verification of the feasibility of methods for assessing all impurities, provision of the certified value traceability. The results of infrared Fourier spectrometry confirm the authenticity of the analysed substance of thiamine hydrochloride. The mass fractions of the main substance were measured using acid- base titration in an aqueous-alcoholic medium, as well as the mass balance method taking into account the contents of sulphate ash, water, related impurities, and residual organic solvents. The expanded uncertainty of the results of measuring the mass fraction of the main substance and groups of impurities was assessed, and the full uncertainty budget was compiled. It has been established that the results of measuring the mass fraction of the main substance in the thiamine hydrochloride substance, determined by the titrimetric method (97.36 ± 0.40)% and the mass balance method (97.37 ± 0.08)%, are consistent with each other within the specified 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 the unit of mass (kilogram) GET 3-2020, State primary measurement standard for units of mass fraction and mass (molar) concentration of water in solid and liquid 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 obtained are relevant for ensuring the measurements uniformity in the quality control of medicines.