Raman spectroscopy, particularly hand-held Raman, is gaining favor as a pharmaceutical QC tool, given its convenience, speed and accuracy. A number of presentations at USP’s annual science meeting in Toronto discussed how hand-held Raman is being successfully used as part of pharmaceutical anticounterfeiting toolkits.
But Raman still lacks some of the ease of method transfer, calibration and validation found with other analytical techniques.
Speaking at USP’s Annual Science meeting, Steven Choquette, Group Leader of the Bioassay Methods Group within the National Institute of Standards and Technology’s Biochemical Science Division, described efforts to provide a standard spectral library for Raman spectroscopy.
The request for such a library first came from the Coblentz Society (for more on that august body, click here )in the 1990s, he said, and efforts to improve validation and calibration for Raman have continued as part of a joint effort with ASTM. For more background, click here.
Raman is a single-beam emission method, Choquette explained, and each vendor’s equipment uses different optical elements and lasers, so Raman spectra from different vendors can look very different from each other, even when analyzing the same very simple molecules. There is a real need for performance validation standards, he said, and for improving traceability, accountability, quality systems and data transfer between different vendors’ systems.
While they may appreciate the fact that Raman provides qualitative answers quickly and without sampling, and that measurements can be taken directly through containers, some end users are troubled by the method's lack of specificity. This is particularly true for first responders who have not been trained in the subtleties of analytical science and who need answers, quickly, out in the field.
Choquette quoted one New York City fireman, “When I point two Raman [devices] at the same stuff [reportedly not the word he used] I should get the same answer,” he said.
At this point, Raman spectral libraries are all vendor-specific and there is no standard spectral library, but, NIST has responded to Coblentz’ request by studying ways to improve calibration and to ‘correct’ for differences between spectra.
Progress is being made, Choquette says, in developing artifact standards to allow for calibration, although NIST must still work out algorithm issues, particularly for system-to-system calibration.
Using a calibrated irradiant light-bulb-like source has always been the traditional way to standardize spectra, but irradiance calibration systems are expensive (according to NIST, they cost $10,000 seven years ago). Although these sources can be used with any laser, they require quite a bit of power, and can be difficult to connect with any given experiment or situation in the field.
NIST has developed a less expensive alternative artifact method, using fluorescent glass Standard Reference Materials to facilitate calibration in the field. Although each glass must be matched with one specific laser, they cost a fraction of what calibrated irradiant sources cost. In a 2002 article, NIST said the first chromium-doped SRM (number 2241, designed to operate with red lasers at about 785 nm) cost about $500 and could be used repeatedly.
Since then additional SRM’s have been developed for FT Raman and for use with blue, green and near-infrared lasers.
Overall, Choquette says, continued progress will be important as Raman gains users in forensics and other fields. Vendors also realize the value of standardization and are participating in the research.
Ultimately, he says, the goal would be generating a community-supported Raman spectroscopy library, which could be used by academicians, industry and government scientists, forensics specialists and first-responders alike.
And what about that New York City fireman? Said Choquette at the conclusion of his talk, “I couldn’t agree with him more.”
We’ll have more on this work on our web site soon. For a brief raw videotaped interview with Steven Choquette, just posted on YouTube, click here.
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