Open Access Peer-reviewed Review

Unveiling molecular secrets: Raman spectroscopy as a versatile tool for advanced analysis and investigation in forensic science and pharmaceuticals

Main Article Content

Md. Dipu Ahmed corresponding author
Kazi Madina Maraz
Saikot Mazumder


The conventional technologies used for identifying, investigating, and analyzing illegal drugs, explosives, and fibers in forensic science often involve destructive methods, preventing re-analysis of evidence. Conversely, a non-destructive approach is crucial for drug characterization, synthesis route development, and identification of counterfeit and adulterated pharmaceuticals. Raman spectroscopy, renowned for its rapid, non-destructive, and cost-effective nature, has emerged as the predominant technique in forensic and pharmaceutical applications. Its inelastic light scattering properties enable drug identification, minimize forensic toxicology and criminalistics, and ensure pharmaceutical product quality. This review explores the analysis of cocaine, RDX, HMX, PETN and TNT in forensic science, where Raman spectroscopy proves invaluable in detecting and quantifying drugs and explosives, deciphering synthesis routes, identifying manufacturing labs, and unveiling trafficking patterns and distribution networks. Additionally, it examines the analysis of acyclovir, ciprofloxacin, and active pharmaceutical ingredients (APIs) in the pharmaceutical industry, offering insights for quality control, combating counterfeit and adulterated products, and facilitating real-time process monitoring. Despite limitations, recent advances in data analysis techniques position Raman spectroscopy as a versatile and promising tool for sample analysis, investigation, and determination in both forensic science and pharmaceuticals, illuminating the path towards enhanced analytical capabilities in these fields.

Raman spectroscopy, Forensic analysis, drug and explosive identification, pharmaceutical analysis, drug development, Counterfeit and Adulterated pharmaceuticals

Article Details

How to Cite
Ahmed, M. D., Maraz, K. M., & Mazumder, S. (2023). Unveiling molecular secrets: Raman spectroscopy as a versatile tool for advanced analysis and investigation in forensic science and pharmaceuticals. Materials Engineering Research, 5(1), 291-305.


  1. Das RS, Agrawal YK. Raman spectroscopy: Recent advancements, techniques and applications. Vibrational Spectroscopy. 2011, 57(2): 163-176.
  2. Suzuki EM and Buzzing P. Applications of Raman spectroscopy in forensic science. I: Principles, comparison to infrared spectroscopy, and instrumentation. Forensic Sci Rev. 2018, 30(2): 111-135.
  3. Weber A, Hoplight B, Ogilvie R, et al. Innovative Vibrational Spectroscopy Research for Forensic Application. Analytical Chemistry. 2023, 95(1): 167-205.
  4. Ott CE, Arroyo LE. Transitioning surface-enhanced Raman spectroscopy (SERS) into the forensic drug chemistry and toxicology laboratory: Current and future perspectives. Wiley Interdisciplinary Reviews: Forensic Science. 2023: e1483.
  5. Kranenburg RF, Verduin J, de Ridder R, et al. Performance evaluation of handheld Raman spectroscopy for cocaine detection in forensic case samples. Drug Testing and Analysis. 2021, 13(5): 1054-1067.
  6. Vankeirsbilck T, Vercauteren A, Baeyens W, et al. Applications of Raman spectroscopy in pharmaceutical analysis. TrAC Trends in Analytical Chemistry. 2002, 21(12): 869-877.
  7. Shah KC, Shah MB, Solanki SJ, et al. Recent advancements and applications of Raman spectroscopy in pharmaceutical analysis. Journal of Molecular Structure. 2023, 1278: 134914.
  8. Wang W ting, Zhang H, Yuan Y, et al. Research Progress of Raman Spectroscopy in Drug Analysis. AAPS PharmSciTech. 2018, 19(7): 2921-2928.
  9. Ekins S. Pharmaceutical applications of Raman spectroscopy. 2007: John Wiley & Sons.
  10. Paudel A, Raijada D, Rantanen J. Raman spectroscopy in pharmaceutical product design. Advanced Drug Delivery Reviews. 2015, 89: 3-20.
  11. Das A, Guo H. Raman spectroscopy, in Reference Module in Earth Systems and Environmental Sciences. 2022, Elsevier.
  12. Gilbert AS. Vibrational, Rotational and Raman Spectroscopy, Historical Perspective. Encyclopedia of Spectroscopy and Spectrometry. Published online 2017: 600-609.
  13. Long DA, Long D. The Raman effect: a unified treatment of the theory of Raman scattering by molecules. Vol. 8. 2002: Wiley Chichester.
  14. Tan P, Hu C, Dong J, et al. Polarization properties, high-order Raman spectra, and frequency asymmetry between Stokes and anti-Stokes scattering of Raman modes in a graphite whisker. Physical Review B. 2001, 64(21).
  15. Kauffmann TH, Kokanyan N, Fontana MD. Use of Stokes and anti‐Stokes Raman scattering for new applications. Journal of Raman Spectroscopy. 2018, 50(3): 418-424.
  16. Parker SF. A review of the theory of Fourier-transform Raman spectroscopy. Spectrochimica Acta Part A: Molecular Spectroscopy. 1994, 50(11): 1841-1856.
  17. Mosca S, Conti C, Stone N, et al. Spatially offset Raman spectroscopy. Nature Reviews Methods Primers. 2021, 1(1).
  18. Chaichi A, Prasad A, Gartia M. Raman Spectroscopy and Microscopy Applications in Cardiovascular Diseases: From Molecules to Organs. Biosensors. 2018, 8(4): 107.
  19. Zhu X, Xu T, Lin Q, et al. Technical Development of Raman Spectroscopy: From Instrumental to Advanced Combined Technologies. Applied Spectroscopy Reviews. 2013, 49(1): 64-82.
  20. Wolverson D. Raman spectroscopy. Characterization of Semiconductor Heterostructures and Nanostructures. Published online 2008: 249-288.
  21. Li YS, Church JS. Raman spectroscopy in the analysis of food and pharmaceutical nanomaterials. Journal of Food and Drug Analysis. 2014, 22(1): 29-48.
  22. Zhu X, Xu T, Lin Q, et al. Technical development of Raman spectroscopy: from instrumental to advanced combined technologies. Applied Spectroscopy Reviews. 2014, 49(1): 64-82.
  23. Xu J, He Q, Xiong Z, et al. Raman Spectroscopy as a Versatile Tool for Investigating Thermochemical Processing of Coal, Biomass, and Wastes: Recent Advances and Future Perspectives. Energy & Fuels. 2020, 35(4): 2870-2913.
  24. Doty KC, Lednev IK. Raman spectroscopy for forensic purposes: Recent applications for serology and gunshot residue analysis. TrAC Trends in Analytical Chemistry. 2018, 103: 215-222.
  25. Mojica ER, Dai Z. New Raman spectroscopic methods’ application in forensic science. Talanta Open. 2022, 6: 100124.
  26. Casey T, Mistek E, Halámková L, et al. Raman spectroscopy for forensic semen identification: Method validation vs. environmental interferences. Vibrational Spectroscopy. 2020, 109: 103065.
  27. Muehlethaler C, Leona M, Lombardi JR. Review of Surface Enhanced Raman Scattering Applications in Forensic Science. Analytical Chemistry. 2015, 88(1): 152-169.
  28. Penido CAFO, Pacheco MTT, Zângaro RA, et al. Identification of Different Forms of Cocaine and Substances Used in Adulteration Using Near‐infrared Raman Spectroscopy and Infrared Absorption Spectroscopy. Journal of Forensic Sciences. 2014, 60(1): 171-178.
  29. Kay KXE, Atabaki AH, Ng WB, et al. Identification of illicit street drugs with swept‐source Raman spectroscopy. Journal of Raman Spectroscopy. 2022, 53(7): 1321-1332.
  30. de Oliveira Penido CAF, Pacheco MTT, Lednev IK, et al. Raman spectroscopy in forensic analysis: identification of cocaine and other illegal drugs of abuse. Journal of Raman Spectroscopy. 2016, 47(1): 28-38.
  31. D’Elia V, Montalvo G, Ruiz CG, et al. Ultraviolet resonance Raman spectroscopy for the detection of cocaine in oral fluid. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2018, 188: 338-340.
  32. D’Elia V, Montalvo G, Ruiz CG. Analysis of street cocaine samples in nasal fluid by Raman spectroscopy. Talanta. 2016, 154: 367-373.
  33. Claybourn M, Ansell M. Using Raman Spectroscopy to solve crime: inks, questioned documents and fraud. Science & Justice. 2000, 40(4): 261-271.
  34. Hernández B, Coïc Y, Pflüger F, et al. All characteristic Raman markers of tyrosine and tyrosinate originate from phenol ring fundamental vibrations. Journal of Raman Spectroscopy. 2015, 47(2): 210-220.
  35. Cialla-May D, Krafft C, Rösch P, et al. Raman Spectroscopy and Imaging in Bioanalytics. Analytical Chemistry. 2021, 94(1): 86-119.
  36. Hackshaw KV, Miller JS, Aykas DP, et al. Vibrational Spectroscopy for Identification of Metabolites in Biologic Samples. Molecules. 2020, 25(20): 4725.
  37. Loureiro PEG, Fernandes AJS, Furtado FP, et al. UV‐resonance Raman micro‐spectroscopy to assess residual chromophores in cellulosic pulps. Journal of Raman Spectroscopy. 2010, 42(5): 1039-1045.
  38. Adhikari S, Ampadu EK, Kim M, et al. Detection of Explosives by SERS Platform Using Metal Nanogap Substrates. Sensors. 2021, 21(16): 5567.
  39. Wackerbarth H, Salb C, Gundrum L, et al. Detection of explosives based on surface-enhanced Raman spectroscopy. Applied Optics. 2010, 49(23): 4362.
  40. Chung JH, Cho SG. Standoff Raman spectroscopic detection of explosive molecules. Bulletin of the Korean Chemical Society. 2013, 34(6): 1668-1672.
  41. Al-Saidi WA, Asher SA, Norman P. Resonance Raman Spectra of TNT and RDX Using Vibronic Theory, Excited-State Gradient, and Complex Polarizability Approximations. The Journal of Physical Chemistry A. 2012, 116(30): 7862-7872.
  42. Almaviva S, Botti S, Cantarini L, et al. Ultrasensitive RDX detection with commercial SERS substrates. Journal of Raman Spectroscopy. 2013, 45(1): 41-46.
  43. Gupta N, Dahmani R. AOTF Raman spectrometer for remote detection of explosives. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2000, 56(8): 1453-1456.
  44. Botti S, Cantarini L, Palucci A. Surface‐enhanced Raman spectroscopy for trace-level detection of explosives. Journal of Raman Spectroscopy. 2010, 41(8): 866-869.
  45. Abdallah A, Mahmoud A, Mokhtar M, et al. Raman spectroscopic and advanced signal processing analyses for real time standoff detection and identification of explosives. Optical and Quantum Electronics. 2022, 54(4).
  46. Jesus JIS da S de, Löbenberg R, Bou-Chacra NA. Raman Spectroscopy for Quantitative Analysis in the Pharmaceutical Industry. Journal of Pharmacy & Pharmaceutical Sciences. 2020, 23(1): 24-46.
  47. Vankeirsbilck T, Vercauteren A, Baeyens W, et al. Applications of Raman spectroscopy in pharmaceutical analysis. TrAC Trends in Analytical Chemistry. 2002, 21(12): 869-877.
  48. Ahmed MD, Maraz KM, Shahida S, et al. A review on the synthesis, surface modification and drug delivery of nanoparticles. Global Journal of Engineering and Technology Advances. 2021, 8(2): 32-45.
  49. Farquharson S. Pharmaceutical applications of Raman spectroscopy. 2014.
  50. Strachan CJ, Rades T, Gordon KC, et al. Raman spectroscopy for quantitative analysis of pharmaceutical solids. Journal of Pharmacy and Pharmacology. 2007, 59(2): 179-192.
  51. Khan Z, Javed F, Shamair Z, et al. Current developments in esterification reaction: A review on process and parameters. Journal of Industrial and Engineering Chemistry. 2021, 103: 80-101.
  52. Simon LL, Simone E, Abbou Oucherif K. Crystallization process monitoring and control using process analytical technology. Process Systems Engineering for Pharmaceutical Manufacturing. Published online 2018: 215-242.
  53. Yu L. Applications of process analytical technology to crystallization processes. Advanced Drug Delivery Reviews. 2004, 56(3): 349-369.
  54. Boiret M, Ginot YM. Counterfeit detection of pharmaceutical tablets with transmission Raman spectroscopy. Spectroscopy Europe. 2011, 23(6): 6.
  55. Luczak A, Kalyanaraman R. Portable and benchtop Raman technologies for product authentication and counterfeit detection. Raman Spectroscopy: Tools, Techniques, and Applications, 2018: 8.
  56. Dégardin K, Guillemain A, Roggo Y. Comprehensive Study of a Handheld Raman Spectrometer for the Analysis of Counterfeits of Solid-Dosage Form Medicines. Journal of Spectroscopy. 2017, 2017: 1-13.
  57. Witkowski MR. The use of Raman spectroscopy in the detection of counterfeit and adulterated pharmaceutical products. American Pharmaceutical Review. 2005, 8(1): 56-62.
  58. D. Patel B, J. Mehta P. An Overview: Application of Raman Spectroscopy in Pharmaceutical Field. Current Pharmaceutical Analysis. 2010, 6(2): 131-141.
  59. Chen X, Stoneburner K, Ladika M, et al. High-Throughput Raman Spectroscopy Screening of Excipients for the Stabilization of Amorphous Drugs. Applied Spectroscopy. 2015, 69(11): 1271-1280.
  60. Wei Y, Dattachowdhury B, Vangara KK, et al. Excipients That Facilitate Amorphous Drug Stabilization. Excipient Applications in Formulation Design and Drug Delivery. Published online 2015: 463-495.
  61. Breitkreuz J, De Beer T, Florin-Muschert S, et al. Stabilization of amorphous drugs; are crystalline inorganic excipients a way forward?
  62. Sahoo A, Suryanarayanan R, Siegel RA. Stabilization of Amorphous Drugs by Polymers: The Role of Overlap Concentration (C*). Molecular Pharmaceutics. 2020, 17(11): 4401-4406.
  63. He Y, Tang L, Wu X, et al. Spectroscopy: The Best Way Toward Green Analytical Chemistry? Applied Spectroscopy Reviews. 2007, 42(2): 119-138.
  64. Zhu X, Xu T, Lin Q, et al. Technical Development of Raman Spectroscopy: From Instrumental to Advanced Combined Technologies. Applied Spectroscopy Reviews. 2013, 49(1): 64-82.
  65. Hou PY, Ager J, Mougin J, et al. Limitations and Advantages of Raman Spectroscopy for the Determination of Oxidation Stresses. Oxidation of Metals. 2011, 75(5-6): 229-245.
  66. Skoulika SG, Georgiou CA. Rapid Quantitative Determination of Ciprofloxacin in Pharmaceuticals by Use of Solid-State FT-Raman Spectroscopy. Applied Spectroscopy. 2001, 55(9): 1259-1265.
  67. Skoulika SG, Georgiou CA. Rapid, Noninvasive Quantitative Determination of Acyclovir in Pharmaceutical Solid Dosage Forms through Their Poly(Vinyl Chloride) Blister Package by Solid-State Fourier Transform Raman Spectroscopy. Applied Spectroscopy. 2003, 57(4): 407-412.
  68. Pelletier MJ. (Ed.). Analytical applications of Raman spectroscopy (Vol. 427). Oxford: Blackwell science, 1999.
  69. Eberhardt K, Stiebing C, Matthäus C, et al. Advantages and limitations of Raman spectroscopy for molecular diagnostics: an update. Expert Review of Molecular Diagnostics. 2015, 15(6): 773-787.
  70. Saletnik A, Saletnik B, Puchalski C. Overview of Popular Techniques of Raman Spectroscopy and Their Potential in the Study of Plant Tissues. Molecules. 2021, 26(6): 1537.
  71. Tuschel D. Raman spectroscopy and polymorphism. Spectroscopy. 2019, 34(3): 10-21.
  72. Durickovic I. Using Raman spectroscopy for characterization of aqueous media and quantification of species in aqueous solution. Applications of Molecular Spectroscopy to Current Research in the Chemical and Biological Sciences, 2016, 405.
  73. Farber C, Sanchez L, Rizevsky S, et al. Raman Spectroscopy Enables Non-Invasive Identification of Peanut Genotypes and Value-Added Traits. Scientific Reports. 2020, 10(1).
  74. Cebeci-Maltaş D, Alam MA, Wang P, et al. Photobleaching profile of Raman peaks and fluorescence background. European Pharmaceutical Review. 2017, 22(6): 18-21.
  75. Ember KJI, Hoeve MA, McAughtrie SL, et al. Raman spectroscopy and regenerative medicine: a review. npj Regenerative Medicine. 2017, 2(1).
  76. West MJ, Went MJ. Detection of drugs of abuse by Raman spectroscopy. Drug Testing and Analysis. 2010, 3(9): 532-538.
  77. Dutta A. Fourier Transform Infrared Spectroscopy. Spectroscopic Methods for Nanomaterials Characterization. Published online 2017: 73-93.
  78. Sala A, Anderson DJ, Brennan PM, et al. Biofluid diagnostics by FTIR spectroscopy: A platform technology for cancer detection. Cancer Letters. 2020, 477: 122-130.
  79. Fahelelbom KM, Saleh A, Al-Tabakha MMA, et al. Recent applications of quantitative analytical FTIR spectroscopy in pharmaceutical, biomedical, and clinical fields: A brief review. Reviews in Analytical Chemistry. 2022, 41(1): 21-33.
  80. Zhang J, Li B, Wang Q, et al. Application of Fourier transform infrared spectroscopy with chemometrics on postmortem interval estimation based on pericardial fluids. Scientific Reports. 2017, 7(1).
  81. Daéid NN. FORENSIC SCIENCES | Systematic Drug Identification. Encyclopedia of Analytical Science. Published online 2005: 471-480.
  82. Mbughuni MM, Jannetto PJ, Langman LJ. Mass spectrometry applications for toxicology. Ejifcc. 2016, 27(4): 272.
  83. Trufelli H, Palma P, Famiglini G, et al. An overview of matrix effects in liquid chromatography–mass spectrometry. Mass Spectrometry Reviews. 2010, 30(3): 491-509.
  84. Mogollón NGS, Quiroz-Moreno CD, Prata PS, et al. New Advances in Toxicological Forensic Analysis Using Mass Spectrometry Techniques. Journal of Analytical Methods in Chemistry. 2018, 2018: 1-17.
  85. Perez ER, Knapp JA, Horn CK, et al. Comparison of LC–MS-MS and GC–MS Analysis of Benzodiazepine Compounds Included in the Drug Demand Reduction Urinalysis Program. Journal of Analytical Toxicology. 2016, 40(3): 201-207.
  86. Fiorentin TR, Fogarty M, Limberger RP, et al. Determination of cutting agents in seized cocaine samples using GC–MS, GC–TMS and LC–MS/MS. Forensic Science International. 2019, 295: 199-206.