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

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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


Figure 4: Confusion matrix for amino acid subset.
Amino acids. Of the 198 test materials, 12 were amino acids. Figure 4 shows p-value ranges for the pairings of amino acids. The green indicates p-values ≥0.1, a more stringent qualification than the test device's normal threshold of 0.05 for a pass result. For all amino acids, the test device correctly verified each material. The test device also correctly rejected nonmatching materials, with p-values ≤1 x 10–8 .


Figure 5: Confusion matrix for organic solvent subset.
Solvents. Test materials also included 15 organic solvents. Figure 5 shows p-value ranges for the test pairings of these solvents. The green area indicates p-values ≥0.1, again, a more stringent qualification than the test device's normal "pass" threshold of 0.05. For this category, the test device correctly verified each material. It also correctly rejected nonmatching materials, with p-values ≤1 x 10–8 , as indicated by red squares in Figure 5.


Figure 6: Confusion matrix for long-chain hydrocarbon subset.
Long-chain hydrocarbons. The p-values for 13 long-chain hydrocarbons are shown in Figure 6. Unlike the other categories of test substances discussed previously, some of these pairings resulted in higher p-values when a method was tested against a similar material in this class of compounds. For larger molecules such as these, the Raman signal corresponding to the long hydrocarbon chain portion of the molecule can dominate the signal making spectral features arising from other functional groups difficult to detect. This is in contrast to small molecules where single atomic or functional group substitutions are easily detected (e.g. acetone/methyl ethyl ketone and calcium sulfate/magnesium sulfate).


Categories of materials.
In almost all cases, the long-chain hydrocarbon pairings produced exclusive (completely selective), pass verdicts with p-values >0.1, indicated by green in Figure 6. The one exception was the magnesium stearate–sorbitan monopalmitate pairing. In this case, the Raman signal from the long-chain hydrocarbon (differing between the two materials by only one carbon) overwhelms differences present in the rest of the molecule. About half of the negative pairings produced very low p-values ≤1 x 10–8 , indicated by red in Figure 6. Nineteen pairings of long-chain hydrocarbons resulted in p-values in the range of 0.01 to 0.1 (yellow in Figure 6). Off-diagonal p-values in this range represent cases in which clear gaps in selectivity between methods exist (p-value >0.05) or where the pairings are not so far removed, lying in the 0.01–0.05 range, that there is risk for inadequate selectivity. It is important to identify materials like these during method validation to identify potential false positives and assess their degree of risk. Another group, the 54 pairings indicated by orange in Figure 6, produced p-values in the range 1 x 10–8 to 0.01 which are of significantly less concern during method validation and robustness testing.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
26%
Attracting a skilled workforce
29%
Obtaining/maintaining adequate financing
14%
Regulatory compliance
31%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Report: Pfizer Makes $101 Billion Offer to AstraZeneca
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Source: Pharmaceutical Technology,
Click here