The Study On Detection Methods Of Solid Drug Constituents Based On Terahertz Time-Domain Spectroscopy

Terahertz time domain spectroscopy(THz-TDS),as a burgeoning technology of spectral analysis,has been widely investigated in many fields.Moreover,its application in the domain of medical detection has become a research focus,especially in the region of pharmaceutical analysis,for its exclusive advantages of causing no ironization demage to materials and being sensitive to the collective modes of motion in medicine(lattice vibration,isomeric configuration difference,etc).The paper focused on the region of pharmaceutical production and supervision,and applied the terahertz technology to the study of identification and analysis of solid pharmaceutical constituents.The terahertz response to different components,such as the unique peaks,the overlapping peaks and the absence of absorption peaks,were analyzed.Then the technique of spectrum analysis,such as the angle of vector subspace and spectrum decomposition,including indirect hard modeling(IHM),were presented.Finally,taking the solid drug samples(select active pharmaceutical ingredients,such as Gliclazide,Carbamazepine and Rifampicin,mix with Lactose monohydrate,Microcrystalline Cellulose and Magnesium Stearate)as the object for validation.The main work and innovations of this thesis are as follows:(1)In order to reveal the physical meaning of the THz response and improve the accuracy and interpretability of the algorithm,the THz absorption spectra of solid pharmaceutical components,such as Gliclazide and so on,were investigated,as well as the relationship between the spectral features and the motion patterns of chemical structures.The analysis of time domain spectroscopy has laid the foundation for the identification of the constituents and the recogntion of absorption peak provides positive guidance for the detection method based on graph decomposition.(2)There is often necessary to determine whether the drug composition is consistent with the description or formula in the practical application.Therefore,the identification of drug components and the detection of unknown compounds other than formula were studied.In order to solve the problem that the qualitative analysis methods generally utilized in the THz-TDS detection are mostly used for the classification of substances and the recognition effect of mixture components are limited,the identification method of multi-component mixtures were studied,focusing on pattern recognition technology of the angle of vector-subspace.In order to verify the feasibility of the algorithm on multi-compornent identification,three mixtures of Gliclazide,Carbamazepine and Rifampicin were detected.Then the effect of characteristics and concentration of the component on the recognition result were discussed.Subsequently,the technique was used to solve the problem that the component in the drug is replaced by some unknown substance.In addition,the prototype system and the application for mixtures analysis of the component identificaiton software based on THz-TDS were described.(3)According to the demand of the content detection on drug ingredients,the study of the method for detection of drug component based on THz-TDS were carried out,mainly to the consitituent whose spectrum with unique absorption peaks,the overlapping peaks and no distinct peaks respectively.Because of the inherent characteristics of physical contact between the unique waveform structure of THz spectral data and ingredient comcentration,the study of the method based on spectral decomposition was developed,and the technique of indirect hard modeling was discussed particularly.Taking the characteristic of THz spectrum into account,the parametric model of IHM algorithm was improved to solve the accuracy problem when the parametric model ultilized to THz spectrum.Then three mixtures of Gliclazide,Carbamazepine and Rifampicin were investigated.Finally the sensitivity of the algorithm to the number of training samples was discussed.The spectrum characteristic of components in solid drug can be characterized by the unique absorption peaks,the overlapping peaks and the absence of absorption peaks,and the THz time domain spectroscopy research and analytical work of the ingredient whose spectrum with those spectral features were carried out.The progress and achievements of this study can be used for reference in the application of terahertz time domain spectroscopy in the detection of drug constituents.