Application Of PH-dependent SERS Spectroscopy Combined With Chemometrics Methods In Rapid Drug Detection

Nowadays there is growing concern about the adulation of synthetic drugs in traditional Chinese medicine or botanical dietary supplements(DBS),because some manufactures have illegally adulterated BDS with more than one kind of pharmacologically similar chemicals at a same time in.Those chemicals often are structural analogues with trace amount making it difficult to distinguish them soly by using routine methods.HPLC,GC,and LC-MS have been frequently used to analysis of complex systems like this.Although these methods are accurate,reliable with high sensetivity,they were not suitable for on-site detection because of the complex operation process,long time of analysis procedure,and expensive equipment.In this work,we use the dynamic surface ehanced Raman scattering spectroscopy combined with two kind of chemometrics methods,i.e.,spectral barcodes and two dimensional correlation spectroscopy to reduce the complexity analysis the variation of spectral features,and able to achieve on-stie detection of adulated analogues in BDS.This study consists of two parts: 1)Firstly,investigation of the effect of varying pH on SERS spectra of twelve chemicals which were often adulterated in BDS were performed.Based on the result of classification,the spectra under different pH conditions were covert into spectral barcodes then used to establish barcodes database.2)The DSERS method was used to real-time monitor the distinct pH-induced spectral evolution process.After that,complex variations in pH-dependent spectral sets were interpreted by 2DCOS.So,a combinative strategy of DSERS and 2DCOS analysis was established and was used to distinguish structural analogues in their mixture.The results were as follows: 1)the SERS performance of 12/7 chemicals are sensitive to surrounding pH conditions,respectively are Caffeine,Theophylline,Theobromine,Metformin,rosiglitazone,Metformin hydrochloride,Sodium aminosalicylate,Diprophylline.The chemicals of Phenformin hydrochloride,Furosemide,Propranolole hydrochloride,Niacin,Phentolamine mesilate are unsensitive to pH variation.The spectral barcodes of twelve chemcials were established by using the similarity of 0.9 as the threshold then used to identification of three components of caffeine,theophylline and theobromine under acidic conditions was realized by using the standard spectrum library.2)In addition,Density Functional Theory(DFT)was used to make the structure optimization and vibration analysis,then identify the vibration assignment of Raman and SERS spectra in different p H conditions.3)The detection conditions of established DSERS-2DCOS method were optimized and the the optimization results are as follows: the concentration of silver colloid was 5 times,the laser power was 150 mW,the detection position was located ar the edge of the droplet,and the optimal initial pH of the mixture of samples and silver gels was 5.0.4)According to the two dimensional correlation maps,the characteristic across peaks of three chemicals was identity respectively.The characteristic across peaks centred at ?(686,678)and ?(1324,1293)belong to Theophylline,peaks centred at ?(648,640)??(1327,1311)are derived from Caffeine,and peaks centred at ?(640,617)and ?(1319,1311)are assigned to Theobromine.5)More over the LOD of three analogues in BDS were 0.05 % for Theophylline,0.05% Caffeine,and 0.01 % for Theobromine.In short,we put forward a strategy that combines pH-dependent DSERS with 2DCOS in analogous mixture analysis at the same time,which is exemplified by three analogues of theophylline,caffeine and theobromine adulterated in botanical dietary supplements(BDS).In this study,the pH-dependent Dynamic SERS combined with 2DCOS method was successfully to detect analogous adulterants in BDS.The newly established DSERS-2DCOS method is simple,high sensitive and specific,which dose not need pre-separation procedure and can be used to realize rapid on-site detection of adulterants in BDS.