FT-IR: Offering Flexibility for Today's Chemists

As one of the many tools in the infrared arsenal, Fourier transform-infrared spectroscopy (FT-IR) has found various uses in several industries, for applications requiring rapid and reliable analysis. This month's Technology Forum takes a look at one of the pharmaceutical industry's favorite workhorses, and what future uses are in store for the technique. Our participants this month are: Richard A. Larsen, scientific applications manager at Jasco, Inc.; John Coates, an industry consultant; John M. Chalmers, chemistry professor at the University of Nottingham, U.K., and industry consultant; and Ashok Cholli, chemistry professor at the University of Massachusetts at Lowell.

What are some of the "hot" applications of FT-IR spectroscopy in the pharmaceutical or organic chemical industries?

(Cholli) In-situ monitoring for process chemistry, and hyphenated techniques involving IR for separating and identifying the compounds.

(Larsen) For pharmaceutical applications, the FDA's PAT (process analytical technology) initiative is demanding on-line/at-line applications for various analysis methods - particularly using FT-NIR instrumentation and compact, stand-alone mid-IR instruments. The ability to provide rapid kinetics analysis capability for organic/polymer applications also is an important "new" area for FT-IR analysis. Infrared imaging is finding several uses in both the organic chemical and pharmaceutical industries. As the instrumentation becomes more integrated into the laboratory, it is becoming increasingly critical to develop "dedicated" instruments with specific analytical methods for specific applications.

(Coates) Many of the FT-IR companies have made instruments targeted at raw material characterization, and often some form of specialized sampling and software is involved.

Reaction monitoring has been another area of focus in the pharma industry for FT-IR, this time mainly in the area of mid-IR. Instruments customized for these applications feature special insertion probes and reaction-monitoring software. These applications range from bench-top applications in the pure drug discovery/research areas to pilot plant monitoring. The latter is used to deduce the optimum conditions for production and also to aid in scale-up to production.

Vapor phase measurements have been made with FT-IR systems, and the two areas of interest here have been the drying process and the solvent recovery processes.

Formulated products are a final area where FT-IR can find a good niche. This is both in the area of simple end-product assay for certain dosage forms, and for tablet homogeneity.

What other industries currently are making use of the technique?

(Cholli) Plastics, gas industries, biotech, petroleum, and wine and beer manufacturing companies use FT-IR consistently.

(Larsen) Polymers, semiconductors, and specialty chemicals come to mind. Almost every industry that requires analysis of organic and organometallic compounds can utilize infrared spectroscopy.

(Chalmers) There is a high level of interest and research into the potential of FT-IR imaging for medical and pathological diagnostics. A significant amount of this work is being done with FT-IR microscope systems that use infrared radiation emanating from a synchrotron as their source. Other industries include food, materials, paper/pulp, packaging, life sciences, and automotive.

(Coates) The oil and petroleum industry - from lube oil blending, to individual additives, to used oil analysis, which also is used by transportation and heavy equipment companies, as well as by the military.

The polymer and plastics industry is a classical industry for FT-IR, where again the technique can be applied from the basic raw materials and monomers, to the final polymers, and on to the fully formulated products.

Consumer product industries include personal care products, soaps, and detergents, as well as food and beverages.

In the semiconductor and high tech materials industries, applications range from the monitoring of production gases and plasma processes, to measurements on silicon wafers, both in the raw form and the final and intermediate processed forms.

FT-IR offers significant time-savings when compared with traditional IR techniques. What other advantages does it offer?

(Larsen) Other advantages for FT-IR instrumentation include increased signal-to-noise, higher resolution capability, superior wavelength reproducibility, greater flexibility for numerous applications, and higher sensitivity for extremely low concentrations of compounds.

(Coates) Versatility and flexibility; the ability to handle solid, liquid, and gas samples, and even others including plasma emissions; the ability to accept a wide range of accessories and sample-handling devices; and the ability to handle difficult samples with a low energy throughput. FT-IR also can be configured with some quite exotic optics and detector systems that provide remarkable results from very small or highly absorbing samples; the FT-IR microscope is a good case in which FT-IR has a distinct advantage.

(Chalmers) FT-IR can provide superior spectral resolution and wavenumber precision and reproducibility, which enable the effective use of many other sampling techniques including inter-alia FT-IR microscopy, imaging, photoacoustic spectroscopy, diffuse reflection, certain time-resolved studies, and remote sensing.

When is the technique not appropriate to utilize?

(Larsen) When there are greater than 6–8 compounds in a mixture, it can be extremely difficult to develop meaningful information from the sample. Samples containing a high amount of water also can require specialty methods for analysis that might not include FT-IR. However, even in these cases, the instrumentation can be combined with SFC and/or HPLC instrumentation as well as TG, DSC, and GC instruments.

(Coates) Because FT-IR is quoted to have great sensitivity, some think that it extends to all types of analyses, including the determination of trace quantities of materials in water solutions. You can determine gases and vapors at ppm, and even ppb levels in air because the interferences are small. However, water is a huge interference in the liquid phase, and the ability to measure organics or other solutes at ppm levels in water directly is simply impractical without some form of extraction or special sampling aid. Handling water solutions in the infrared can be tough, and all types of interferences from salts, pH variations, and temperature can occur. Things have to be controlled very well when you are working with low concentrations of solutes in water. Sometimes these interferences cause perturbations in the spectrum that look like spectral information, and sometimes people try to interpret these as real information.

You can measure metal compounds and metals in certain states (usually indirectly) with FT-IR, but you really cannot do direct elemental analysis. Metals and metal ions can have a big impact on counter ions and chelate structures, and one can measure the presence or the influence of the metal by inference, but you are not measuring the ion directly as you would by atomic absorption or ICP emission.

(Chalmers) FT-IR can be limited in its application to inorganics, but this is more of a limitation on mid-infrared generally, as opposed to FT-IR in particular. Such limitations can be overcome with appropriate far-infrared FT-IR equipment. Also, the technique has limited success when coupled with HPLC.

How do hyphenated techniques enhance FT-IR’s analytical abilities?

(Cholli) Hyphenated techniques allow chemists to identify structures of separated compounds by combining analyses with separation techniques.

(Chalmers) If we count FT-IR coupled to optical microscopy, then the enhancement is enormous, widely commercialized, and utilized throughout industry and academia. One can characterize what can be seen down to approximately the 10-micron spatial resolution level.

Chromatography techniques add selectivity to FT-IR’s specificity, and vice versa, particularly GC-FTIR. TGA coupled with FT-IR also enables evolved species characterization associated with thermal events. 

Are stand-alone systems becoming obsolete in favor of integrated instruments?

(Larsen) There still are numerous applications for stand-alone applications (see previous answers). 

(Coates) To some extent yes…where it makes sense. People are tending to buy down, and to buy an instrument for a set of applications. We see less of the full-blown research units being used now. The price of an instrument has come down to a point today where the FT-IR becomes a commodity item.

The integrated instrument sometimes is perceived to be limited in functionality, and consequently “expensive.” We are seeing integrated microscope systems, but there still are a lot of simple-to-use, standard FT-IR instruments being sold. Many of the current instruments use smart sampling in which accessories are designed to “plug-in” and the instrument identifies the accessory and the system becomes configured for that accessory.

Anything else you'd like to add?

(Larsen) FT-IR will always have a home in the analytical laboratory due to its flexibility and compatibility with various other analysis methods.

(Cholli) Over the years, FT-IR instruments have gone through many changes so that they have become inexpensive, versatile, and easy to use. Techniques have been integrated with new systems in which there is no (or minimal) sample preparation required for routine analysis in QA/QC, synthesis, or analytical laboratories.