Spectroscopy provides molecular fingerprints and spatially resolved chemical information for APIs, excipients, polymorphs, contaminants, and formulations.
This decision-focused guide explains the scientific measurement basis, when to use it, its limitations, sample amount considerations, competing methods, FDA-facing concerns, and common mistakes.
Raman, FTIR, and IR imaging measure molecular vibrational information. Raman is often strong for polymorph differentiation and aqueous samples; FTIR is useful for functional groups, material identity, and ATR surface analysis; imaging adds spatial distribution.
Use spectroscopy for raw-material ID, polymorph and cocrystal differentiation, contaminant identification, tablet/component mapping, low-level API in formulations, counterfeit work, and method development when a spectral fingerprint is specific.
Fluorescence can interfere with Raman, FTIR can saturate or require thickness/dilution control, spectra may overlap in mixtures, and chemometric models can fail outside their training space. Spectroscopy may need XRPD, DSC, chromatography, or NMR for confirmation.
Amount depends on spot size, mapping area, matrix, and required detection limit. IR imaging can be applied to very small samples, including features on the order of tens of microns; larger representative material may be required for mapping, validation, or cGMP method work.
XRPD, NMR, chromatography, mass spectrometry, microscopy, and thermal analysis can compete or complement spectroscopy depending on whether the question is molecular identity, crystal phase, spatial distribution, or quantitative assay.
FDA cares about method specificity, representative sampling, validated chemometric models where used, robustness to sample preparation and matrix changes, and whether the spectral method is suitable for release, stability, or identity testing.
Common mistakes include using library matches without confirming matrix effects, ignoring fluorescence, overfitting chemometrics, mapping too small an area, and claiming polymorph identity without proving spectral specificity against realistic alternatives.
Triclinic uses spectroscopy for practical material identification, solid-form screening, functional-group confirmation, contaminant comparison, phase mapping, and rapid lot or sample comparisons. Raman, FTIR, IR imaging, and UV/Vis are applied when spectral fingerprints can distinguish materials, support incoming-material or investigation work, or provide orthogonal evidence alongside diffraction, chromatography, microscopy, or thermal analysis.
The table below lists the specific platforms, brands, models, software, detectors, and capability notes relevant to this service area.
| Instrument or platform | Brand, model, software, or detector | Additional capabilities and use |
|---|---|---|
| Dispersive Raman microscopy | Renishaw inVia Raman microscope with DMLM Leica microscope, 785 nm laser, and CCD detector | Chemical imaging, confocal microsampling, polymorph discrimination, carbon-nanotube characterization, and spatial component mapping. |
| FT-Raman | Thermo NXT FT-Raman module interfaced to Nicolet 6700 FT-IR spectrometer; 1064 nm Nd:YAG laser; InGaAs detector; OMNIC v.9.7.46 with spectral libraries | Micro and macro Raman sampling, reduced fluorescence for selected samples, library matching, and non-destructive molecular fingerprinting. |
| Low-frequency Raman | Ondax THz-Raman system with probe | Stokes and anti-Stokes signals from +/-5 cm-1 to 200 cm-1, or 150 GHz to 6 THz, for lattice-mode/polymorph-sensitive measurements. |
| Infrared imaging | Thermo iN10 MX with Picta 1.5.141 software | IR chemical imaging, ATR/reflection/transmission sampling, microsampling, real-time particle identification, and distribution mapping. |
| FT-IR | Thermo iS50 Model 60825 and Nicolet 6700; ATR, diffuse reflectance, transmission, gas cell; DTGS detector; OMNIC v.9.7.46 software | Functional-group identification, spectral-library matching, gas-cell/TGA-IR evolved-gas analysis, and organic/inorganic material identification. |
| UV/VIS | PerkinElmer Lambda 25 | Quantitative analyte measurement, kinetic studies, and HPLC/dissolution detection support where UV response is suitable. |
This example shows why spectroscopy can be more than a library match. The legacy spectroscopy page describes Raman and IR methods for molecular fingerprinting, polymorph differentiation, contaminant identification, and chemical imaging. Chemical imaging converts many spatially resolved spectra into a map of where components are located within a sample.
These examples include technical resources, regulatory guidances, or literature relevant to the technique. Download buttons are placed at the bottom-left of each example.
Author: Triclinic Labs
Publication date: 2019
Abstract: This white paper describes how low-frequency Raman can distinguish polymorphic forms using lattice-mode information not always available in conventional mid-frequency Raman. It supports using Raman as an orthogonal solid-form tool when XRPD, DSC, or FTIR are inconclusive.
Author: Triclinic Labs
Publication date: April 2023
Abstract: This application note evaluates acetaminophen spray-dried dispersions by dissolution testing followed by post-dissolution PXRD and low-frequency Raman mapping, showing how Raman imaging can connect chemical identity and spatial distribution in formulation-relevant samples.
Author: International Council for Harmonisation / FDA
Publication date: 2024
Abstract: FDA notes that ICH Q2(R2) and Q14 describe validation and development principles for analytical procedures used to assess drug substance and drug product quality. These guidances frame FDA expectations for specificity, accuracy, precision, range, robustness, lifecycle management, and fit-for-purpose method evidence.
Use this technique when its evidence better matches the sample, matrix, or development decision.
View techniqueUse this technique when its evidence better matches the sample, matrix, or development decision.
View techniqueUse this technique when its evidence better matches the sample, matrix, or development decision.
View techniqueUse this technique when its evidence better matches the sample, matrix, or development decision.
View techniqueUse this technique when its evidence better matches the sample, matrix, or development decision.
View techniqueUse this technique when its evidence better matches the sample, matrix, or development decision.
View technique
Tell Triclinic what sample you have, what decision the data must support, what prior data are available, and whether cGMP, release, validation, or regulatory documentation is required.
