Verification Methods for 198 Common Raw Materials Using a Handheld Raman Spectrometer - Pharmaceutical Technology

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Verification Methods for 198 Common Raw Materials Using a Handheld Raman Spectrometer
Using handheld Raman spectroscopy, methods were developed and evaluated for 198 substances widely used as raw materials.

Pharmaceutical Technology
Volume 33, Issue 10, pp. 72-82

Results and discussion

The handheld Raman material-identity verification system shows a pass result whenever test of a method against a material produces a p-value ≥0.05. In general, testing a method against the "wrong" material produces a p-value far less than 0.05, resulting in a fail.

Figure 2: Histogram of p-values for true positive testing and false positive testing of 198 materials.
Figure 2 provides a summary in histogram form of the p-values generated in this study for all pairings of the 198 materials tested. The green bars represent results obtained when testing materials against methods corresponding to the same materials (true positive testing), and the red bars represent analyses achieved when testing materials against other methods (false-positive testing). To view both sets of results in the same graph, the y-axis of the histogram represents the fraction of samples in each bin rather than the total frequency of samples in each bin. The results from true positive testing, in green, are all above the pass threshold with p-values ranging from 0.052 to > 0.5. Though the false-positive testing did reveal a few negative samples with values as high as 0.15, well above the pass threshold and therefore false positives, the frequency with which this occurred is so low that negative samples with p-values > 0.05 are not visible in the histogram. Conversely, negative samples presented in the histogram reveal that more than 99% of pairings where methods were tested against a different material, the p-value obtained was less than 10–13 , considerably less than the pass threshold, and a definitive fail result. This demonstrates the extreme degree of selectivity achievable with handheld Raman spectroscopy.

Figure 3: Confusion matrix summary of p-values for device challenges on 198 materials.
The data in the histogram in Figure 2 were also encoded as a confusion matrix (see Figure 3), thus providing a different view of the information. Figure 3 contains 198 rows and 198 columns (39,204 method–test material pairings), color coded red for p-values <0.05 (corresponding to "fail" results) and green for p-values ≥ 0.05 (corresponding to "pass" results). The green along the diagonal in Figure 3 shows where the test device declared pass results when a method was tested against its corresponding material. The red shown on the vast majority of off-diagonal positions indicates where the device declared a fail result when testing a method against the wrong material. As can be seen in Figure 3, for all but six pairings, the test device indicated pass when the material's method was tested against the same material, and fail when tested against all others.

The false-positive results for the six pairings shown in Figure 3 are results of the extremely high similarity in composition and/or molecular structure of the materials in each pair. One example is safflower oil, which has a very high concentration of linoleic aicd. Other examples are povidone and crospovidone which have the same structure except for a cross linkage in crospovidone. The slight differences between the materials in each pair do not result in significant differences in their Raman spectra.

To enhance the granularity of p-value results, the range was more finely divided in the following compound class studies, allowing a more detailed evaluation of the differentiating capability of the device's embedded decision algorithms.


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