Bevz O. Scientific substantitation of certification of pharmacopoeia standard samples using thermal analysis methods

The thesis is devoted to the issues of synthesis of material for certification (CM) of impurities of active pharmaceutical ingredients and the use of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) for certification of pharmacopoeial reference standards of the State Pharmacopoeia of Ukraine (SPhU RSs). Ornidazole-diol, ornidazole-epoxide, and pregabalin impurity D of high yield and purity were obtained following the optimisation of the procedures for their synthesis. The impurities were characterised by TGA and DSC. A mathematical model is proposed to describe the final part of the thermogram. A statistically sound procedure for determining the drying end time is substantiated. Metrological requirements for the results of the test for volatile impurities by TGA are formulated. The obtained results met the stringent requirements for the tasks of SPhU RSs certification. TGA was used for homogeneity evaluation and establishment of the certified value of CM. A CM for the qualification of the TGA method was selected. Metrological requirements for the results of the purity determination by DSC are advanced. A CM for the qualification of the DSC method was selected; its purity, melting temperature and enthalpy of melting were characterised simultaneously. The DSC method was used in the certification of 4 SPhU RS intended for the verification of the melting temperature determination with the characterisation of the enthalpy of melting. The TGA method was used to determine the CM purity as an alternative method. 14 SPhU RSs for assays and SPhU RSs intended for the qualification of TGA and DSC methods were certified