Research Progress of Raman Spectroscopy and Raman Imaging in Pharmaceutical
Analysis

Jie      Ren; Shijie      Mao; Jidong      Lin; Ying      Xu; Qiaoqiao      Zhu; Ning      Xu
Abstract

The analytical investigation of the pharmaceutical process monitors the critical process parameters of the drug, beginning from its development until marketing and post-marketing, and appropriate corrective action can be taken to change the pharmaceutical design at any stage of the process. Advanced analytical methods, such as Raman spectroscopy, are particularly suitable for use in the field of drug analysis, especially for qualitative and quantitative work, due to the advantages of simple sample preparation, fast, non-destructive analysis speed and effective avoidance of moisture interference. Advanced Raman imaging techniques have gradually become a powerful alternative method for monitoring changes in polymorph distribution and active pharmaceutical ingredient distribution in drug processing and pharmacokinetics. Surface-enhanced Raman spectroscopy (SERS) has also solved the inherent insensitivity and fluorescence problems of Raman, which has made good progress in the field of illegal drug analysis. This review summarizes the application of Raman spectroscopy and imaging technology, which are used in the qualitative and quantitative analysis of solid tablets, quality control of the production process, drug crystal analysis, illegal drug analysis, and monitoring of drug dissolution and release in the field of drug analysis in recent years.
Keywords: Raman spectroscopy, raman imaging, pharmaceutical analysis, coherent raman scattering spectroscopy, surface-enhanced raman spectroscopy, active pharmaceutical ingredients.
[1] 
Neuberger S, Neusüß C. Determination of counterfeit medicines by Raman spectroscopy: Systematic study based on a large set of model tablets. J Pharm Biomed Anal  2015; 112: 70-8.
[http://dx.doi.org/10.1016/j.jpba.2015.04.001] [PMID:  25956227] 
[2] 
Dégardin K, Roggo Y, Been F, Margot P. Detection and chemical profiling of medicine counterfeits by Raman spectroscopy and chemo-metrics. Anal Chim Acta  2011; 705(1-2): 334-41.
[http://dx.doi.org/10.1016/j.aca.2011.07.043] [PMID:  21962376] 
[3] 
Wang WT, Zhang H, Yuan Y, Guo Y, He SX. Research progress of Raman spectroscopy in drug analysis. AAPS PharmSciTech  2018; 19(7): 2921-8.
[http://dx.doi.org/10.1208/s12249-018-1135-8] [PMID:  30091063] 
[4] 
Farber C, Mahnke M, Sanchez L, Kurouski D. Advanced spectroscopic techniques for plant disease diagnostics: A review. Trends Analyt Chem  2019; 118: 43-9.
[http://dx.doi.org/10.1016/j.trac.2019.05.022] 
[5] 
Alula MT, Mengesha ZT, Mwenesongole E. Advances in surface-enhanced Raman spectroscopy for analysis of pharmaceuticals: A review. Vib Spectrosc  2018; 98: 50-63.
[http://dx.doi.org/10.1016/j.vibspec.2018.06.013] 
[6] 
Pinzaru SC, Pavel I, Leopold N, Kiefer W. Identification and characterization of pharmaceuticals using Raman and surface-enhanced Raman scattering. J Raman Spectrosc  2004; 35(5): 338-46.
[http://dx.doi.org/10.1002/jrs.1153] 
[7] 
Ellis DI, Cowcher DP, Ashton L, O’Hagan S, Goodacre R. Illuminating disease and enlightening biomedicine: Raman spectroscopy as a diagnostic tool. Analyst (Lond)  2013; 138(14): 3871-84.
[http://dx.doi.org/10.1039/c3an00698k] [PMID:  23722248] 
[8] 
Ayala AP. Polymorphism in drugs investigated by low wavenumber Raman scattering. Vib Spectrosc  2007; 45(2): 112-6.
[http://dx.doi.org/10.1016/j.vibspec.2007.06.004] 
[9] 
Vankeirsbilck T, Vercauteren A, Baeyens W, et al. Applications of Raman spectroscopy in pharmaceutical analysis. Trends Analyt Chem  2002; 21(12): 869-77.
[http://dx.doi.org/10.1016/S0165-9936(02)01208-6] 
[10] 
Sacré PY, Deconinck E, Saerens L, et al. Detection of counterfeit Viagra® by Raman microspectroscopy imaging and multivariate analy-sis. J Pharm Biomed Anal  2011; 56(2): 454-61.
[http://dx.doi.org/10.1016/j.jpba.2011.05.042] [PMID:  21715121] 
[11] 
Das RS, Agrawal YK. Raman spectroscopy: Recent advancements, techniques and applications. Vib Spectrosc  2011; 57(2): 163-76.
[http://dx.doi.org/10.1016/j.vibspec.2011.08.003] 
[12] 
De Beer TR, Bodson C, Dejaegher B, et al. Raman spectroscopy as a process analytical technology (PAT) tool for the in-line monitoring and understanding of a powder blending process. J Pharm Biomed Anal  2008; 48(3): 772-9.
[http://dx.doi.org/10.1016/j.jpba.2008.07.023] [PMID:  18799281] 
[13] 
Farquharson A, Gladding Z, Ritchie G, et al. Drug content uniformity: Quantifying loratadine in tablets using a created Raman excipient spectrum. Pharmaceutics  2021; 13(3): 309.
[http://dx.doi.org/10.3390/pharmaceutics13030309] [PMID:  33673552] 
[14] 
Kandpal LM, Cho BK, Tewari J, Gopinathan N. Raman spectral imaging technique for API detection in pharmaceutical microtablets. Sens Actuators B Chem  2018; 260: 213-22.
[http://dx.doi.org/10.1016/j.snb.2017.12.178] 
[15] 
Juan Ade J, Tauler R, Dyson R. Spectroscopic imaging and chemometrics: A powerful combination for global and local sample analysis. Trends Analyt Chem  2004; 23: 70-9.
[16] 
Ling J, Weitman SD, Miller MA, Moore RV, Bovik AC. Direct Raman imaging techniques for study of the subcellular distribution of a drug. Appl Opt  2002; 41(28): 6006-17.
[http://dx.doi.org/10.1364/AO.41.006006] [PMID:  12371563] 
[17] 
Mamián-López M, Poppi RJ. SERS hyperspectral imaging assisted by MCR-ALS for studying polymeric microfilms loaded with parace-tamol. Microchem J  2015; 123: 243-51.
[http://dx.doi.org/10.1016/j.microc.2015.07.003] 
[18] 
Yu B, Ge M, Li P, Xie Q, Yang L. Development of surface-enhanced Raman spectroscopy application for determination of illicit drugs: Towards a practical sensor. Talanta  2019; 191: 1-10.
[http://dx.doi.org/10.1016/j.talanta.2018.08.032] [PMID:  30262036] 
[19] 
Zeng J, Zhao W, Yue S. Coherent Raman scattering microscopy in oncology pharmacokinetic research. Frontiers in Pharmacology  2021; 12: 630167.
[20] 
Raman CV. A change of wave-length in light scattering. Nature  1928; 121(3051): 619-9.
[http://dx.doi.org/10.1038/121619b0] 
[21] 
Smith E, Dent G. Modern raman spectroscopy - A practical approach (Smith/modern raman spectroscopy - A practical approach).  More Advanced Raman Scattering Techniques John Wiley & Sons, Ltd. 2005; pp. 181-202.
[http://dx.doi.org/10.1002/0470011831] 
[22] 
Long DA. Introduction to Raman spectroscopy. Cambridge: Royal Soc Chemistry 2005.
[23] 
Ember KJI, Hoeve MA, McAughtrie SL, et al. Raman spectroscopy and regenerative medicine: A review. Regen Med  2017; 2: 10.
[24] 
Delhaye M, Dhamelincourt P. Raman microprobe and microscope with laser excitation. J Raman Spectrosc  1975; 3(1): 33-43.
[http://dx.doi.org/10.1002/jrs.1250030105] 
[25] 
Garrett NL, Godfrey L, Lalatsa A, et al. Detecting polymeric nanoparticles with coherent anti-stokes Raman scattering microscopy in tissues exhibiting fixative-induced autofluorescence. In: Periasamy A, So PTC, Konig K, Eds. Multiphoton Microscopy In the Biomedi-cal Sciences Xv.  2015.
[26] 
Muller M, Schins JM, Nastase N, Wurpel S, Brakenhoff FGJ. Imaging the chemical composition and thermodynamic state of lipid mem-branes with multiplex CARS microscopy. Biophys J  2002; 82(1): 175A-A.
[27] 
Volkmer A. Coherent Raman scattering microscopy. Springer Berlin Heidelberg 2010.
[28] 
Lohumi S, Kim MS, Qin J, Cho B-K. Raman imaging from microscopy to macroscopy: Quality and safety control of biological materials. Trends Analyt Chem  2017; 93: 183-98.
[http://dx.doi.org/10.1016/j.trac.2017.06.002] 
[29] 
Rebiere H, Ghyselinck C, Lempereur L, Brenier C. Investigation of the composition of anabolic tablets using near infrared spectroscopy and Raman chemical imaging. Drug Test Anal  2016; 8(3-4): 370-7.
[http://dx.doi.org/10.1002/dta.1843] [PMID:  26198290] 
[30] 
Waffo Tchounga CA, Sacre PY, Ciza P, et al. Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic. J Pharm Biomed Anal  2021; 194: 113761.
[http://dx.doi.org/10.1016/j.jpba.2020.113761] [PMID:  33234414] 
[31] 
Francis AT, Nguyen TT, Lamm MS, et al. In situ stimulated Raman scattering (SRS) microscopy study of the dissolution of sustained-release implant formulation. Mol Pharm  2018; 15(12): 5793-801.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00965] [PMID:  30362772] 
[32] 
Figueroa B, Nguyen T, Sotthivirat S, et al. Detecting and quantifying microscale chemical reactions in pharmaceutical tablets by stimulat-ed Raman scattering microscopy. Anal Chem  2019; 91(10): 6894-901.
[http://dx.doi.org/10.1021/acs.analchem.9b01269] [PMID:  31009215] 
[33] 
Šaši&#263; S, Prusnick T. Fast Raman chemical imaging of tablets with non-flat surfaces. Int J Pharm  2019; 565: 143-50.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.004] [PMID:  31071419] 
[34] 
Arruabarrena J, Coello J, Maspoch S. Raman spectroscopy as a complementary tool to assess the content uniformity of dosage units in break-scored warfarin tablets. Int J Pharm  2014; 465(1-2): 299-305.
[http://dx.doi.org/10.1016/j.ijpharm.2014.01.027] [PMID:  24508332] 
[35] 
Fülöp G, Balogh A, Farkas B, et al. Homogenization of Amorphous Solid Dispersions Prepared by Electrospinning in Low-Dose Tablet Formulation. Pharmaceutics  2018; 10(3): E114.
[http://dx.doi.org/10.3390/pharmaceutics10030114] [PMID:  30072667] 
[36] 
Boiret M, Rutledge DN, Gorretta N, Ginot YM, Roger JM. Application of independent component analysis on Raman images of a phar-maceutical drug product: Pure spectra determination and spatial distribution of constituents. J Pharm Biomed Anal  2014; 90: 78-84.
[http://dx.doi.org/10.1016/j.jpba.2013.11.025] [PMID:  24333706] 
[37] 
Boiret M, de Juan A, Gorretta N, Ginot YM, Roger JM. Setting local rank constraints by orthogonal projections for image resolution anal-ysis: Application to the determination of a low dose pharmaceutical compound. Anal Chim Acta  2015; 892: 49-58.
[http://dx.doi.org/10.1016/j.aca.2015.08.031] [PMID:  26388474] 
[38] 
Eksi-Kocak H, Ilbasmis Tamer S, Yilmaz S, Eryilmaz M, Boyaci IH, Tamer U. Quantification and spatial distribution of salicylic acid in film tablets using FT-Raman mapping with multivariate curve resolution. Asian J Pharm Sci  2018; 13(2): 155-62.
[http://dx.doi.org/10.1016/j.ajps.2017.07.010] [PMID:  32104388] 
[39] 
Jiang H-Y, Ding C, Wang Y, et al. Determination of acetaminophen spatial distribution and content in tablets using confocal micro-Raman spectroscopy mapping. J Nanopart Res  2020; 22(9): 265.
[http://dx.doi.org/10.1007/s11051-020-04970-z] 
[40] 
Su Y, Zhang Y, Wang Y, et al. Spatial distribution and content determination of Ganoderic acid F in tablets using confocal Raman micro-spectroscopy. J Ambient Intell Humaniz Comput  2021; 12: 3505-14.
[41] 
Sanhueza MI, Meléndrez MF, Plessing C, et al. Raman microimaging as an analytical technique for simultaneous quantification and local-ization of active principles in pharmaceutical solid dosage forms. J Raman Spectrosc  2020; 51(4): 649-59.
[http://dx.doi.org/10.1002/jrs.5833] 
[42] 
Wardrop J, Law D, Qiu Y, Engh K, Faitsch L, Ling C. Influence of solid phase and formulation processing on stability of Abbott-232 tablet formulations. J Pharm Sci  2006; 95(11): 2380-92.
[http://dx.doi.org/10.1002/jps.20679] [PMID:  16892210] 
[43] 
Li X, Zhi F, Hu Y. Investigation of excipient and processing on solid phase transformation and dissolution of ciprofloxacin. Int J Pharm  2007; 328(2): 177-82.
[http://dx.doi.org/10.1016/j.ijpharm.2006.08.012] [PMID:  16978809] 
[44] 
Sun Z, Ya N, Adams RC, Fang FS. Particle size specifications for solid oral dosage forms: A regulatory perspective. Am Pharm Rev  2010; 13(4): 68-73.
[45] 
Frosch T, Wyrwich E, Yan D, Popp J, Frosch T. Fiber-array-based raman hyperspectral imaging for simultaneous, chemically-selective monitoring of particle size and shape of active ingredients in analgesic tablets. Molecules  2019; 24(23): E4381.
[http://dx.doi.org/10.3390/molecules24234381] [PMID:  31801249] 
[46] 
Fule R, Paithankar V, Amin P. Hot melt extrusion based solid solution approach: Exploring polymer comparison, physicochemical char-acterization and in-vivo evaluation. Int J Pharm  2016; 499(1-2): 280-94.
[http://dx.doi.org/10.1016/j.ijpharm.2015.12.062] [PMID:  26746801] 
[47] 
Markus T. Ely Dr, Carvajal MT, Pinal R. Improvement of the dissolution rate of poorly soluble drugs by solid crystal suspensions. Mol Pharm  2011; 8: 727-35.
[48] 
Reitz E, Vervaet C, Neubert RHH, Thommes M. Solid crystal suspensions containing griseofulvin--preparation and bioavailability test-ing. Eur J Pharm Biopharm  2013; 83(2): 193-202.
[http://dx.doi.org/10.1016/j.ejpb.2012.09.012] [PMID:  23108185] 
[49] 
Pawar JN, Fule RA, Maniruzzaman M, Amin PD. Solid crystal suspension of Efavirenz using hot melt extrusion: Exploring the role of crystalline polyols in improving solubility and dissolution rate. Mater Sci Eng C  2017; 78: 1023-34.
[http://dx.doi.org/10.1016/j.msec.2017.04.055] [PMID:  28575936] 
[50] 
Reddy JP, Jones JW, Wray PS, Dennis AB, Brown J, Timmins P. Monitoring of multiple solvent induced form changes during high shear wet granulation and drying processes using online Raman spectroscopy. Int J Pharm  2018; 541(1-2): 253-60.
[http://dx.doi.org/10.1016/j.ijpharm.2018.02.021] [PMID:  29481947] 
[51] 
Nomura K, Titapiwatanakun V, Hisada H, Koide T, Fukami T. In situ monitoring of the crystalline state of active pharmaceutical ingredi-ents during high-shear wet granulation using a low-frequency Raman probe. Eur J Pharm Biopharm  2020; 147: 1-9.
[http://dx.doi.org/10.1016/j.ejpb.2019.12.004] [PMID:  31841690] 
[52] 
Huang Y, Dai W-G. Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B  2014; 4(1): 18-25.
[http://dx.doi.org/10.1016/j.apsb.2013.11.001] [PMID:  26579360] 
[53] 
Sandrien J. Review: Physical chemistry of solid dispersions. J Pharm Pharmacol  2009; 61: 1571-86.
[54] 
Vo CL-N, Park C, Lee B-J. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J
 Pharm Biopharm  2013; 85((3 Pt B)(3, Part B)): 799-813.
[http://dx.doi.org/10.1016/j.ejpb.2013.09.007] [PMID: 24056053] 
[55] 
Luebbert C, Klanke C, Sadowski G. Investigating phase separation in amorphous solid dispersions via Raman mapping. Int J Pharm  2018; 535(1-2): 245-52.
[http://dx.doi.org/10.1016/j.ijpharm.2017.11.014] [PMID:  29133204] 
[56] 
Novakovic D, Isomäki A, Pleunis B, et al. Understanding dissolution and crystallization with imaging: A surface point of view. Mol Pharm  2018; 15(11): 5361-73.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00840] [PMID:  30247922] 
[57] 
Porquez JG, Slepkov AD. Application of spectral-focusing-CARS microscopy to pharmaceutical sample analysis. AIP Adv  2018; 8(9): 095213.
[http://dx.doi.org/10.1063/1.5027273] 
[58] 
Sarri B, Canonge R, Audier X, et al. Discriminating polymorph distributions in pharmaceutical tablets using stimulated Raman scattering microscopy. J Raman Spectrosc  2019; 50(12): 1896-904.
[http://dx.doi.org/10.1002/jrs.5743] 
[59] 
Tres F, Treacher K, Booth J, et al. Real time Raman imaging to understand dissolution performance of amorphous solid dispersions. J Control Release  2014; 188: 53-60.
[60] 
Melian ME, Munguía AB, Faccio R, Palma S, Domínguez L. The impact of solid dispersion on formulation, using confocal micro raman spectroscopy as tool to probe distribution of components. J Pharm Innov  2017; 13(1): 58-68.
[http://dx.doi.org/10.1007/s12247-017-9306-9] 
[61] 
Chang Y, Hu C, Yang R, et al. A Raman imaging-based technique to assess HPMC substituent contents and their effects on the drug re-lease of commercial extended-release tablets. Carbohydr Polym  2020; 244: 116460.
[http://dx.doi.org/10.1016/j.carbpol.2020.116460] [PMID:  32536397] 
[62] 
Tarn D, Ashley CE, Xue M, Carnes EC, Zink JI, Brinker CJ. Mesoporous silica nanoparticle nanocarriers: Biofunctionality and biocom-patibility. Acc Chem Res  2013; 46(3): 792-801.
[http://dx.doi.org/10.1021/ar3000986] [PMID:  23387478] 
[63] 
Tang F, Li L, Chen D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv Mater  2012; 24: 1504-34.
[64] 
Lee S, Kwon JA, Park KH, Jin CM, Joo JB, Choi I. Controlled drug release with surface-capped mesoporous silica nanoparticles and its label-free in situ Raman monitoring. Eur J Pharm Biopharm  2018; 131: 232-9.
[http://dx.doi.org/10.1016/j.ejpb.2018.08.012] [PMID:  30165104] 
[65] 
Feizpour A, Marstrand T, Bastholm L, Eirefelt S, Evans CL. Label-free quantification of pharmacokinetics in skin with stimulated raman scattering microscopy and deep learning. J Invest Dermatol  2021; 141(2): 395-403.
[http://dx.doi.org/10.1016/j.jid.2020.06.027] [PMID:  32710899] 
[66] 
Sepp K, Lee M, Bluntzer MTJ, Helgason GV, Hulme AN, Brunton VG. Utilizing stimulated raman scattering microscopy to study intra-cellular distribution of label-free ponatinib in live cells. J Med Chem  2020; 63(5): 2028-34.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01546] [PMID:  31829628] 
[67] 
Burr DS, Fatigante WL, Lartey JA, et al. Integrating SERS and PSI-MS with dual purpose plasmonic paper substrates for on-site illicit drug confirmation. Anal Chem  2020; 92(9): 6676-83.
[http://dx.doi.org/10.1021/acs.analchem.0c00562] [PMID:  32255335] 
[68] 
Shao B, Chen D, Zhang J, Wu Y, Sun C. Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater. J Chromatogr A  2009; 1216(47): 8312-8.
[http://dx.doi.org/10.1016/j.chroma.2009.08.038] [PMID:  19825501] 
[69] 
Andersson M, Gustavsson E, Stephanson N, Beck O. Direct injection LC-MS/MS method for identification and quantification of am-phetamine, methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine in urine drug testing. J Chromatogr B Analyt Technol Biomed Life Sci  2008; 861(1): 22-8.
[http://dx.doi.org/10.1016/j.jchromb.2007.11.025] [PMID:  18088576] 
[70] 
Li B, Zhang T, Xu Z, Fang HHP. Rapid analysis of 21 antibiotics of multiple classes in municipal wastewater using ultra performance liquid chromatography-tandem mass spectrometry. Anal Chim Acta  2009; 645(1-2): 64-72.
[http://dx.doi.org/10.1016/j.aca.2009.04.042] [PMID:  19481632] 
[71] 
Viehrig M, Rajendran ST, Sanger K, et al. Quantitative SERS assay on a single chip enabled by electrochemically assisted regeneration: A method for detection of melamine in milk. Anal Chem  2020; 92(6): 4317-25.
[http://dx.doi.org/10.1021/acs.analchem.9b05060] [PMID:  31985206] 
[72] 
Bi L, Wang Y, Yang Y, et al. Highly sensitive and reproducible SERS sensor for biological pH detection based on a uniform gold nano-rod array platform. ACS Appl Mater Interfaces  2018; 10(18): 15381-7.
[http://dx.doi.org/10.1021/acsami.7b19347] [PMID:  29664282] 
[73] 
Dong R, Weng S, Yang L, Liu J. Detection and direct readout of drugs in human urine using dynamic surface-enhanced Raman spectros-copy and support vector machines. Anal Chem  2015; 87(5): 2937-44.
[http://dx.doi.org/10.1021/acs.analchem.5b00137] [PMID:  25634247] 
[74] 
Gheorghe A, van Nuijs A, Pecceu B, et al. Analysis of cocaine and its principal metabolites in waste and surface water using solid-phase extraction and liquid chromatography-ion trap tandem mass spectrometry. Anal Bioanal Chem  2008; 391(4): 1309-19.
[http://dx.doi.org/10.1007/s00216-007-1754-5] [PMID:  18066537] 
[75] 
Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: Recent developments and future needs. Trends Pharmacol Sci  2002; 23(5): 238-45.
[http://dx.doi.org/10.1016/S0165-6147(02)02017-5] [PMID:  12008002] 
[76] 
Fang F, Qi Y, Lu F, Yang L. Highly sensitive on-site detection of drugs adulterated in botanical dietary supplements using thin layer chromatography combined with dynamic surface enhanced Raman spectroscopy. Talanta  2016; 146: 351-7.
[http://dx.doi.org/10.1016/j.talanta.2015.08.067] [PMID:  26695274] 
[77] 
Ma Y, Du YY, Chen Y, et al. Intrinsic Raman signal of polymer matrix induced quantitative multiphase SERS analysis based on stretched PDMS film with anchored Ag nanoparticles/Au nanowires. Chem Eng J  2020; 381: 16.
[http://dx.doi.org/10.1016/j.cej.2019.122710] 
[78] 
Lee KM, Yarbrough D, Kozman MM, et al. Rapid detection and prediction of chlortetracycline and oxytetracycline in animal feed using surface-enhanced Raman spectroscopy (SERS). Food Control  2020; 114: 10.
[http://dx.doi.org/10.1016/j.foodcont.2020.107243] 
[79] 
Drummer OH. Review: Pharmacokinetics of illicit drugs in oral fluid. Forensic Sci Int  2005; 150(2-3): 133-42.
[http://dx.doi.org/10.1016/j.forsciint.2004.11.022] [PMID:  15944053] 
[80] 
Crouch DJ, Day J, Baudys J, et al. Evaluation of saliva/oral fluid
 as an alternate drug testing specimen NIJ Report  2005; 605-13.
[81] 
Allen KR. Screening for drugs of abuse: Which matrix, oral fluid or urine? Ann Clin Biochem  2011; 48(Pt 6): 531-41.
[http://dx.doi.org/10.1258/acb.2011.011116] [PMID:  21885472] 
[82] 
Dana K, Shende C, Huang H, Farquharson S. Rapid analysis of cocaine in saliva by surface-enhanced Raman spectroscopy. J Anal Bioanal Tech  2015; 6(6): 1-5.
[PMID:  26819811] 
[83] 
Li W, Li X, Yang T, Guo X, Song Y. Detection of saliva morphine using surface&enhanced Raman spectroscopy combined with immu-nochromatographic assay. J Raman Spectrosc  2020; 51(4): 642-8.
[http://dx.doi.org/10.1002/jrs.5822] 
[84] 
Tehrani MS, Givianrad MH, Mahoor N. Surfactant-assisted dispersive liquid-liquid microextraction followed by high-performance liquid chromatography for determination of amphetamine and methamphetamine in urine samples. Anal Methods  2012; 4(5): 1357-64.
[http://dx.doi.org/10.1039/c2ay25125f] 
[85] 
Meng J, Tang X, Zhou B, Xie Q, Yang L. Designing of ordered two-dimensional gold nanoparticles film for cocaine detection in human urine using surface-enhanced Raman spectroscopy. Talanta  2017; 164: 693-9.
[http://dx.doi.org/10.1016/j.talanta.2016.10.101] [PMID:  28107992] 
[86] 
Han S, Zhang C, Lin S, Sha X, Hasi W. Sensitive and reliable identification of fentanyl citrate in urine and serum using chloride ion-treated paper-based SERS substrate. Spectrochim Acta A Mol Biomol Spectrosc  2021; 251: 119463.
[http://dx.doi.org/10.1016/j.saa.2021.119463] [PMID:  33493937] 
[87] 
Shende C, Brouillette C, Farquharson S. Detection of codeine and fentanyl in saliva, blood plasma and whole blood in 5-minutes using a SERS flow-separation strip. Analyst (Lond)  2019; 144(18): 5449-54.
[http://dx.doi.org/10.1039/C9AN01087D] [PMID:  31424465] 
[88] 
Fang W, Zhang B, Han FY, et al. On-site and quantitative detection of trace methamphetamine in urine/serum samples with a surface-enhanced Raman scattering-active microcavity and rapid pretreatment device. Anal Chem  2020; 92(19): 13539-49.
[http://dx.doi.org/10.1021/acs.analchem.0c03041] [PMID:  32924435] 
[89] 
Yu B, Cao C, Li P, Mao M, Xie Q, Yang L. Sensitive and simple determination of zwitterionic morphine in human urine based on liquid-liquid micro-extraction coupled with surface-enhanced Raman spectroscopy. Talanta  2018; 186: 427-32.
[http://dx.doi.org/10.1016/j.talanta.2018.04.094] [PMID:  29784383] 
[90] 
Yu B, Li P, Zhou B, Tang X, Li S, Yang L. Sodium chloride crystal-induced SERS platform for controlled highly sensitive detection of illicit drugs. Chemistry  2018; 24(19): 4800-4.
[http://dx.doi.org/10.1002/chem.201800487] [PMID:  29484732] 
[91] 
Sivashanmugan K, Squire K, Tan A, et al. Trace detection of tetrahydrocannabinol in body fluid via surface-enhanced Raman scattering and principal component analysis. ACS Sens  2019; 4(4): 1109-17.
[http://dx.doi.org/10.1021/acssensors.9b00476] [PMID:  30907578] 
[92] 
Mao K, Zhou Z, Han S, et al. A novel biosensor based on Au@Ag core-shell nanoparticles for sensitive detection of methylampheta-mine with surface enhanced Raman scattering. Talanta  2018; 190: 263-8.
[http://dx.doi.org/10.1016/j.talanta.2018.07.071] [PMID:  30172508] 
[93] 
Haddad A, Comanescu MA, Green O, Kubic TA, Lombardi JR. Detection and quantitation of trace fentanyl in heroin by surface-enhanced Raman spectroscopy. Anal Chem  2018; 90(21): 12678-85.
[http://dx.doi.org/10.1021/acs.analchem.8b02909] [PMID:  30247896] 
[94] 
Fedick PW, Pu F, Morato NM, Cooks RG. Identification and confirmation of fentanyls on paper using portable surface enhanced Raman spectroscopy and paper spray ionization mass spectrometry. J Am Soc Mass Spectrom  2020; 31(3): 735-41.
[http://dx.doi.org/10.1021/jasms.0c00004] [PMID:  32126777] 
[95] 
Dies H, Raveendran J, Escobedo C, Docoslis A. Rapid identification and quantification of illicit drugs on nanodendritic surface-enhanced Raman scattering substrates, Sens. Sens Actuators B Chem  2018; 257: 382-8.
[http://dx.doi.org/10.1016/j.snb.2017.10.181] 
[96] 
Hong Y, Zhou X, Xu B, et al. Optoplasmonic hybrid materials for trace detection of methamphetamine in biological fluids through SERS. ACS Appl Mater Interfaces  2020; 12(21): 24192-200.
[http://dx.doi.org/10.1021/acsami.0c00853] [PMID:  32351116] 
[97] 
Shende C, Farquharson A, Brouillette C, Smith W, Farquharson S. Quantitative measurements of codeine and fentanyl on a surface-enhanced Raman-active pad test. Molecules  2019; 24(14): 8.
[http://dx.doi.org/10.3390/molecules24142578] [PMID:  31315188] 
[98] 
Salemmilani R, Mirsafavi RY, Fountain AW, Moskovits M, Meinhart CD. Quantitative surface-enhanced Raman spectroscopy chemical analysis using citrate as an in situ calibrant. Analyst (Lond)  2019; 144(5): 1818-24.
[http://dx.doi.org/10.1039/C8AN02170H] [PMID:  30672922] 
[99] 
Guo L, Wang K, Xu B, et al. A kind of method and kit for detecting fentanyl/morphine compounds. CN111521597A 2020.
[100] 
Dong R, Li S, Lin D, Chen H, Yang L. Progress of the applications of surface-enhanced Raman spectroscopy in illicit drug detection. Scientia Sinica Chimica  2021; 51(3): 294-309.
[http://dx.doi.org/10.1360/SSC-2020-0196] 
[101] 
Huang Y, Xie T, Zou K, et al. Ultrasensitive SERS detection of exhaled biomarkers of lung cancer using a multifunctional solid phase extraction membrane. Nanoscale  2021; 13(31): 13344-52.
[http://dx.doi.org/10.1039/D1NR02418C] [PMID:  34477740] 
Cite As
Current Pharmaceutical Design

Research Progress of Raman Spectroscopy and Raman Imaging in Pharmaceutical Analysis

Abstract
