SubscribeFourier-transform infrared (FTIR), near-infrared (NIR), and Raman are three related analytical techniques for vibrational spectroscopy.
Vibrational spectroscopy is the analysis of molecular properties based on vibrations at the molecular level. Vibrational spectroscopy is known to be highly selective at the molecular level, producing a spectral fingerprint of each compound, thereby being well-suited for raw material and final product identification and verification.
This technical note provides a brief overview of each technology, followed by a tabulated discussion of questions concerning validation and performance.
FTIR
Mid-infrared spectroscopy was historically the most commonly used vibrational technique for material identification and authentication.i In mid-IR, which is often called FTIR due to a popular instrument configuration, light absorption by the material of interest is measured across a range of wavelengths (~ 400 - 4000 cm-1) corresponding to fundamental molecular vibrational modes.
FTIR has exquisite molecular selectivity and the absorptions are strong; however, sample presentation to the instrument has to be accomplished through special sample preparation (e.g. KBr pellets or Nujol mulls) or through use of specialized accessories, such as attenuated total reflectance (ATR) crystals. With few exceptions, the sample of interest must be in direct contact with the instrument and with ATR only a few microns (a thousandth of a millimeter) of material is actually interrogated.
NIR
Near-infrared spectroscopy (NIR) gained favor over the last 20 years largely because of its convenient and relatively large volume sampling.ii NIR characterizes the material based on its absorption in the ~ 4000 - 12500 cm-1 wavelength region, corresponding to vibrational overtone (harmonic) and combination modes. The bands observed in NIR predominantly arise from stretching of O-H, C-H, and N-H bonds, and are greatly broadened relative to their FTIR counterparts. Due to broadening, and the commonality of these substructures across organic molecules, the differences between NIR spectra of different compounds are often very subtle, resulting in a lower inherent molecular selectivity than FTIR.
Raman
In contrast to FTIR and NIR, which involve IR absorption, Raman is a scattering technique. Raman is effective in the 250-2875 cm-1 range and involves a shifting of incident light so is typically called Raman shift. Raman, like FTIR, interrogates fundamental vibrational modes resulting in outstanding molecular selectivity; however Raman is much more attractive in terms of sampling convenience as it can easily be used in a non-contact fashion through many common container materials such as glasses and plastics.iii
Raman is free from interference due to water bands which so dominate FTIR spectra and influence NIR as well. Raman experiments in the past have required extensive knowledge of light collection and amplification techniques -- but the sensitivity of TruScan instrumentation is such that acquisition times in seconds are now the norm with the instrument self adjusting to environmental background conditions. This makes the TruScan version of Raman a technique which incorporates the selectivity of FTIR and the sampling convenience of NIR with independence from some common interferences such as water bands.
| FTIR | Raman | NIR | |
| selectivity | High; directly interpretable spectra | High; directly interpretable spectra | Low; extensive calibration and chemometrics often required to distinguish materials; difficult to interpret directly |
| interference | Measurements strongly influenced by the presence of water | Fluorescence baseline can result in longer measurement times; new lasers such as that used in TruScan greatly reduce sample fluorescence | Measurements influenced by water; signal impacted by physical attributes such as particle hardness, size and shape |
| sampling | KBr. Nujol mulls, or ATR crystals with direct sample contact; fiber optics not readily available | Stand-off sampling through glass and plastics possible; fiber optics common; TruScan has relatively large volume sampling (~2mm spot at the sample plane) | Can measure through some materials such as glass; fiber optics common; large sampling volumes common |
| portability | Typically large laboratory devices, designed for static environment | Typically large, but TruScan is a miniaturized and robust option | Most NIR systems are large and designed for static environment; some cartable options are becoming available |
| method development | Visual examination often used (no development but highly subjective and irreproducible); similarity scores common; chemometric methodologies can also be used | TruScan uses a managed process for method setup and execution; automated data management and user independent statistical analysis | Analysis typically based on chemometric methods; low inherent selectivity and sampling effects makes for laborious and expensive method development |
Conclusions
All three spectroscopic techniques are useful in pharmaceutical applications. FTIR and Raman share the characteristics of being highly selective and therefore quite useful for compound identification testing. Raman's ease of sampling, due to its independence from packaging materials as well as water and humidity, will benefit users who have struggled with applying FTIR and NIR techniques to these applications. The advent of modern electronics and optics have made Raman practical for average users. The technique will likely find a larger role in the pharmaceutical testing laboratory, even moving testing from the lab to the loading dock.
References
- J.A. Ryan, S.V. Compton, M.A. Brooks, D.A.C. Compton, Rapid verification of identity and content of drug formulations using mid-infrared spectroscopy, J. Pharm. Biomed. Anal. 1991, 9, 303-310 and references therein.
- M. Blanco, J. Coello, H. Iturriaga, S. Maspoch, and C. de la Pezuela, Near-infrared spectroscopy in the pharmaceutical industry, Analyst 1998, 123, 135R-150R.
- R.L. McCreery, A.J. Horn, J. Spencer, E. Jefferson, "Noninvasive identification of materials inside USP vials with Raman spectroscopy and a Raman spectral library", J. Pharm. Sci., 1998, 87, 1-8.