Rapid Detection Of Low API Signal Drug By Surface Enhanced Raman Spectroscopy

In the last decades, Raman spectroscopy developed rapidly with its characteristics of fast, simple, nondestructive, high efficiency and so on, which was widely applied in the field of drug screening. However, advances in drug research and manufacturing technology have led to more versatile drugs geared toward low dosage with powerful efficacy. These drugs with low active pharmaceutical ingredient (API) content are insensitive to NRS analysis, or their low Raman scattering coefficients. For both cases, we regard these drugs as Low API-Signal Drugs (LASIDs). This research we want to establish a tailored solution to the analytical problem of LASIDs from normal Raman spectroscopy, Raman mapping to surface enhanced Raman Scattering(SERS) and so on. Moreover, the using of TLC-SERS can be accurately obtained the quantitative and quantitative results, which provided a novel approach to rapid detect the LASIDs.This text contained three sections, their main contents are as follows:1) Using normal Raman spectroscopy(NRS), Infrared spectroscopy(IR), Near-Infrared spectroscopy(NIR) and Raman mapping to screening and characterize the LASIDs.First of all, calculation and comparison the correlation coefficient between LASID and its standard. The lower similarity indicated that the API in these drugs were insensitive to NRS analysis, while the obtained spectra look extremely similar to those of excipients, such as lactose, starch and microcrystalline cellulose (MCC). Moreover, the randomly selected LASIDs were further characterized by IR, NIR and Raman mapping analysis, which also revealed and validated the excipients dominated and often masked API spectral information in LASIDs, and the content uniformity and mixing evenness of these drugs are usually difficult to control.2) To make qualitative analysis of LASIDs by using paper-SERS. Experimental conditions and parameters including paper support matrix, SERS substrate, detection mode, etc., were optimized to establish a rapid and reliable detection model of LASIDs.First, a large quantity of DMF solvent silver sol was deposited on filter paper and selected as SERS substrate for investigating the property of different silver sol. Secondly, the immersion time of silver paper was optimized when soaking 22 h to obtain the highest enhancement performance comparing with the direct distribution droplets. Finally, the detection of four LASlDs shown that this paper-SERS method has strong specificity and good repeatability with their similarity greater than 0.9 to the corresponding standard.3) Using TLC-SERS method to make qualitative and quantitative analysis for API in its corresponding LASID. For qualitative analysis, the support matrix and separation conditions were investigated and optimized to achieve the detection of LASlDs and their structural analogues. For quantitative analysis, the internal standard substance and quantitative model were investigated and optimized to establish a robust model for rosiglitazone maleate(RSG).Firstly, the correlation coefficient between LASID’s and its standard’s SERS spectrum was reached to 0.9 or even higher, which can be effectively distinguished by TLC(Yantai) both in situ and after-separation. For the Glitazones and Azole oxazine and their structural analogues, using their different SERS spectra and Rf values can realize the identification. Moreover, NaSCN, as an internal standard substance, was added into the RSG sample solution and the calibration curve presented a good linearity with a correlation coefficient (R2) of 0.9977. the methodological evaluation by five RSG samples showed that the recovery rates were 97.9%-117.5%, and the RSD was 7.19%, as validated by HPLC result.In this text, the NRS method was applied to screening and defined the LASIDs, meanwhile, the detection of LASIDs was carried out on paper-SERS and TLC-SERS. The used silver paper was easy to carry, simple preparation and remarkable enhancement, combination with SERS technique can accurately detect LASIDs. TLC, with its advantage of in-situ and after-separation, can be gradually done qualitative analysis for LASIDs, even when combined with its separation capacity, more structural analogues can be realized their qualitative and quantitative detection.Therefore, TLC-SERS method has a broad application prospect in the field of drug fast detection with its simple, accurate, and efficient.