Imagine that you’re standing at the loading dock of a laboratory, and a shipment arrives with two clear bags of white powders. One is a pure substance, the other a mixture—but to your eye they look identical. Or pretend that you’re doing quality control for a pharmaceutical company, and you need to check that some tablets have the proper ratios of ingredients—but the pills are already inside the bubble packaging. In either case, you don’t want to open the packages and spoil the product, but you need to identify and quantify the substances present. How can you do this?
To your rescue comes infrared spectroscopy. Fourier transform infrared (FTIR) spectroscopy can assess mixtures in a way that can ascertain the presence of individual components. Meanwhile, near-infrared (NIR, or sometimes FT-NIR) spectroscopy can take advantage of near-infrared light’s ability to pass through transparent packaging and excite the molecules of the substance contained therein. The resulting information from these methods can reveal not only what components are present on a qualitative basis, but in the case of a properly calibrated analysis, it can provide quantitative information about how much of a given substance is present.
FTIR spectroscopy is considered to be the ultimate triage technique, because the process is so straightforward and speedy: you basically present the sample, get an answer, and act on it. The sampling for FTIR can be very flexible, since it has the ability to look at gases, liquids or solids. In the case of mid-IR or NIR wavelengths, sample analysis can even be extended to microscopy. With that extension, one can analyze bulk samples all the way down to micro-sized samples. This is what is needed in a triage situation, like the scenarios with the powders and tablets described above: you need to find actionable information, whatever the situation, and you need it fast.
Here are a couple real-world examples of the versatility and usefulness of infrared spectroscopy:
In this first example, samples came from a crime scene in what was a case of pharmaceutical forensics. A drug given to somebody had caused an adverse effect. The FTIR spectrum of the drug was taken, and the image of all the peaks (shown in Figure 1) was searched against a library. The spectrum did not give a high-quality match against any pharmaceutical sample in the system. The reason for this, it turned out, was because the material was a mixture.
Using an algorithm known as a multi-component search or multi-component mixture analysis, the spectrometer’s processor was able to deconvolute the spectrum.
The algorithm performed a function that might be thought of as analogous to chromatography, but from a vibrational spectroscopy point of view. In this case, four separate spectra were found to comprise the original composite spectrum: ketamine, methamphetamine, procaine and caffeine. (See Figure 2.)
This is a nasty mixture to give to someone! The composite spectrum, shown in black in Figure 1, matches closely with the original sample spectrum. A cursory analysis of the other graphs from Figure 2 illuminates how the spectrum of pure ketamine does not match the spectrum of the sample. This whole analysis only took about one minute from the time the sample was placed on the FTIR spectrometer accessory until the deconvoluted spectrum and the four different component spectra were delivered. (These results were subsequently verified by using GC-MS analysis.)
This second example involved the pharmaceutical combination of oxycodone and acetaminophen (often found as the brand name Percocet). The active pharmaceutical ingredient, or API, is present at a very low concentration. How low? Take a look at the images from the analysis shown in Figure 3. In this case, the oxycodone was only 5 mg out of a full 325 mg tablet. Yet the FT-NIR analysis was able to discern it! Trying to find that small amount of oxycodone in a tablet of acetaminophen is the pharmaceutical analysis equivalent of trying to find a needle in a haystack, and NIR found it.
At the top of this figure, you can see results of four different components that were found. The most prominent image, second from the left with all the green and the yellow in it, is the acetaminophen that is spread throughout the tablet.
On the left hand side is the oxycodone–the tiny little green spots show its slight presence. While it may be a small amount, its spectrum extracted for the compound is very clean. Just a tiny little trace is adequate to deliver good data for an infrared analysis. (The other two images at the top of Figure 3 show the major inactive additives, cellulose and stearic acid.) The main point here is that FTIR spectroscopy was able to show both the homogeneity of the tablet—the acetaminophen and other items are fairly even spread out—and the relative distribution of the oxycodone, which is only about 1.5%. Actually finding the oxycodone even in these low concentration points marks a major benefit for pharmaceutical analysis.
With these examples demonstrating that the technique can identify both pure items and the components of mixtures, it is useful to re-state that this type of FTIR analysis, specifically using light in the near-infrared region, can analyze through a transparent container, like glass jars or plastic bags. When raw materials come in at the loading dock in the form of plastic bags inside a drum, a handheld NIR device can see right through the package. If a tablet is stored in a bubble pack, you don’t need to open those wrappers to do the analysis and risk contamination or spoilage. FTIR and NIR analysis can provide materials identification or look at the uniformity of a tablet or coatings, right through the package.
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