Raman spectroscopy is an analytical technique that provides highly detailed chemical information on a range of samples. It is normally non-destructive, rapid and requires little to no sample preparation. A number of pharmaceutical companies have adopted Raman spectroscopy as an efficient and effective technique for in-process analysis, raw material identification and final product authentication.
Portable and handheld devices are used to qualify that incoming raw materials are both the correct material and meet sufficient quality. The USP and EP presently recognize Raman spectroscopy as a suitable alternative for compendia identification. A common issue with Raman spectroscopy is has been interference from fluorescent molecules, often excipients, frequently present in ‘real world’ samples of interest. If present, fluorescence interference is typically orders of magnitude higher than the Raman signal, preventing successful chemical identification and/ or analysis.
Figure 1. Sodium Alginate 785nm vs 1064nm
Figure 2. Croscarmellose 785nm vs 1064nm
Identification of Pharmaceutical Excipients
Fluorescence interference reduces the signal to the background noise ratio, can considerably increase the acquisition time and reduces the number of peaks available for identification. By rightly selecting the excitation laser wavelength of a Raman spectrometer, fluorescence can be avoided.
Although sensitivity usually improves as laser wavelength shortens fluorescence occurs more frequently at these shorter wavelengths, meaning vital spectral information may not be attainable. Fluorescence from excipients is a common problem associated with handheld Raman analysers using 785 nanometre wavelength laser sources.
Five common excipients used in many pharmaceutical products were analyzed using a 1064 nanometre Rigaku Raman FirstGuard Analyzer and a competitor’s 785 nm system (Figures 1 – 5).
The 785 nm spectra show considerable fluorescence, and is unlikely that it will provide any reliable information about the sample. If correctable, testing times would need to be significantly increased, but even then, the chances of false identification will be substantial. In contrast, the 1064 nanometre spectra are clean and informative, and can be used to produce confident chemical identification.
Figure 3. FirstGuard Handheld Raman Spectrometer
Figure 4. Xantus 2 portable dual wavelength Raman spectrometer
This information has been sourced, reviewed and adapted from materials provided by Rigaku.
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