Construction And Preliminary Application Of Raman Spectroscopy Library Of Pharmaceutical Excipients

QiErYao adverse drug events, poison capsule crisis and abusing of Tween80that tookplace in recent years declared that pharmaceutical excipients were no longer auxiliarymaterials which were inactive and non-toxic. Toxic excipients do great harm to people’ssafety and health, and illegal usage of substandard materials disrupt normal developmentof pharmaceutical market. At present, due to the invention and application of new materialsand dosage forms, a wide variety of pharmaceutical excipients appear on the internationalmarkets. While in the domestic, excipients market is rising at an initial stage. Theimbalances of production level lead to uneven quality of pharmaceutical excipients, andcounterfeit events sometimes happen. It is a great challenge for the analysts to solve theproblem of identification of pharmaceutical excipients in these situations:at source, incirculation or during production. Popularization of detection technology depends on theindicators including rapidity, simplicity, economy and accuracy. There are manypharmaceutical excipients analysis methods such as chemical methods, chromatography,spectroscopy, etc. Among them, the Raman technology is simple, fast, sensitive, withoutsample preparation, in situ testing, feature-rich and have other unique advantages,combined with chemometrics methods which have been widely reported.This paper outlined the core algorithms in the subjects of mass spectrometry andspectroscopy database application. Application of these algorithms in these fields is quitemature. Then, on the basis of collected information of excipients which would be used toconstruct library, Raman spectra of pharmaceutical exicipents were acquired by portableRaman spectrometer. Pretreatments such as cutting, smoothing, baseline correction wereused before construction of the library, then the characteristic Raman bands of theexcipients were interpreted. Finally, the simulation algorithm combined with flowchart ofcharacteristic bands were used for the quantitative identification of unknown samples andthe detection of counterfeit medicines.Part Ι. Overview. Chemometrics applied theories and methods of mathematics andstatistics, chemistry and computer science and other disciplines, maximize useful chemicalinformation through the analysis of chemical data. At present, in the field of massspectrometry and spectroscopy database, sophisticated Chemometric methods are widelyused.MS/MS spectral library search application has become reliable means for proteomics and plant metabolomics research. Spectrum library construction methods are widely usedin archaeological, forensic and structure elucidation process. Appropriate methods can beused for the construction of pharmaceutical excipients library. Raman spectroscopytechnology as a mean of analysing material which is convenient, rapid and non-destructive.Study on application of this technology in the analysis subject is increasing. In this paperRaman spectrum library of pharmaceutical excipients was established by learning from theabove methods, then an effective solution for fast identification of pharmaceuticalexcipients was provided.PartⅡ. Construction of Raman spectrum library of pharmaceutical excipients.As supervision of pharmaceutical excipients strengthened in domestic market, establishingreliable Raman spectrum library is necessary and in line with the reality. Some Ramanspectroscopic databases such as Satler, Thermo Fisher which are expensive, having nointerpretation of Raman bands, and is not suitable for domestic market. In this paper,145pharmaceutical excipients from authentic sources were collected. The number include91kinds of excipients. Information such as names, manufacturers and usage of theseexcipients was collected. All of them have been analysed by Raman spectroscopy. Afterpretreatments of these spectra, peak tables and interpretation of characteristic Raman bandswere summarized. The collected pharmaceutical excipients encompassed the followingeight classes: polysaccharides; polymers; aliphatic hydrocarbon compounds; carboxylicacids and salts; mono-and disaccharides and polyalcohols; amino acids and salts;sulfur-contained inorganic substances; phosphorus-contained inorganic substances; Thenflowcharts were presented based on wavenumber and intensity of the pharmaceuticalexcipients Raman bands.Part Ⅲ. Preliminary application of Raman spectroscopy Library ofpharmaceutical excipients. Nowadays, in domestic markets there co-exist thesephenomena: different technologies were used by manufactures to product the sameexcipient. the capacity of these manufactures not on the same level. Meanwhile somepharmaceutical excipients are not properly named. So it is urgent to strengthen theadministration of the market. In this paper, three pretreatment methods and different HQIvalues were investigated for identification of unknown pharmaceutical excipients. Themost suitable pretreatment method was selected to combine with flowcharts to identifyunknown excipients. Best results were obtained with first derivative and the HQI value was0.9. Furthermore with the number of the excipients in the library increased, the method was still suitable for the identification. On the basis of the Raman spectra, excipients usedin genuine and counterfeit drugs were identified, sometimes PCA was incorporated toidentify the counterfeit drugs.In this paper, Raman spectrometry was used to construct library of pharmaceuticalexcipients and the library was used for identifying unkown pharmaceutical excipients, andit has broad application prospects. Application fields and core algorithms correlated withMS/MS spectrometry and spectroscopy database were summaried. In addition to this,145pharmaceutical excipients were collected, eight categories were divided according to thestructure of the excipients. According to the spectrum interpretation results, characteristicband flowcharts were presented. Furthermore, a relatively complete set of excipientidentification system were established. This paper is more than a simple summary ofpharmaceutical excipients, preliminary application of pharmaceutical excipients librarywas used to solve the realistic problems about how to identify the pharmaceuticalexcipients faster and accurately, and contribute a strength for pharmaceutical excipientsquality supervision.