Instruments attenuated total reflection

FTIR instrumentation is mature. A typical routine mid-IR spectrometer has KBr optics, best resolution of around 1cm-1, and a room temperature DTGS detector. Noise levels below 0.1 % T peak-to-peak can be achieved in a few seconds. The sample compartment will accommodate a variety of sampling accessories such as those for ATR (attenuated total reflection) and diffuse reflection. At present, IR spectra can be obtained with fast and very fast FTIR interferometers with microscopes, in reflection and microreflection, in diffusion, at very low or very high temperatures, in dilute solutions, etc. Hyphenated IR techniques such as PyFTIR, TG-FTIR, GC-FTIR, HPLC-FTIR and SEC-FTIR (Chapter 7) can simplify many problems and streamline the selection process by doing multiple analyses with one sampling. Solvent absorbance limits flow-through IR spectroscopy cells so as to make them impractical for polymer analysis. Advanced FTIR... 

Similar work was performed by Shaw et al.3 in 1999 when they used FT-Raman, equipped with a charge coupled device (CCD) detector (for rapid measurements) as an on-line monitor for the yeast biotransformation of glucose to ethanol. An ATR (attenuated total reflectance) cell was used to interface the instrument to the fermentation tank. An Nd YAG laser (1064 nm) was used to lower fluorescence interference and a holographic notch filter was employed to reduce Rayleigh scatter interference. Various chemometric approaches were explored and are explained in detail in their paper. The solution was pumped continuously through a bypass, used as a window in which measurements were taken. 

A majority of traditional NIR measurements are made on solid materials and these involve reflectance measurements, notably via diffuse reflectance. Likewise, in the mid-IR not all spectral measurements involve the transmission of radiation. Such measurements include internal reflectance (also known as attenuated total reflectance, ATR), external reflectance (front surface, mirror -style or specular reflectance), bulk diffuse reflectance (less common in the mid-IR compared to NIR), and photoacoustic determinations. Photoacoustic detection has been applied to trace-level gas measurements and commercial instruments are available based on this mode of detection. It is important to note that the photoacoustic spectrum is a direct measurement of infrared absorption. While most infrared spectra are either directly or indirectly correlated... 

FT Spectrometers FT spectrometers (Figure 3) differ from scanning spectrometers by the fact that the recorded signal is an interferogram [14] (see Chapter 6.2). They can be coupled to a microscope or macrochamber with an FPA detector. FT chemical imaging systems (CISs) are available for Raman, NIR, and IR spectroscopy. However, they can only be considered as research instruments. For example, most IR imaging systems are FT spectrometers coupled to microscopes. This type of spectrometer allows the acquisition of spectra in reflection, attenuated total reflection (ATR), or transmission mode. 

Identifying pharmaceuticals, whether APIs or excipients used to manufacture products, and the end products themselves is among the routine tests needed to control pharmaceutical manufacturing processes. Pharmacopoeias have compiled a wide range of analytical methods for the identification of pharmaceutical APIs and usually several tests for a product are recommended. The process can be labor-intensive and time-consuming with these conventional methods. This has raised the need for alternative, faster methods also ensuring reliable identification. Of the four spectroscopic techniques reviewed in this book, IR and Raman spectroscopy are suitable for the unequivocal identification of pharmaceuticals as their spectra are compound-specific no two compounds other than pairs of enantiomers or oligomers possess the same IR spectrum. However, IR spectrometry is confronted with some practical constraints such as the need to pretreat the sample. The introduction of substantial instrumental improvements and the spread of attenuated total reflectance (ATR) and IR microscopy techniques have considerably expanded the scope of IR spectroscopy in the pharmaceutical field. Raman spectroscopy,... 

Attenuated total reflectance Eourier-transform infrared (ATR-ETIR) spectroscopy is another technique recently reported to have been applied to the determination of pesticide residues on human skin and residential surfaces (Doran et al., 2000). While this technique gave good results when evaluated in the laboratory for three pesticides at 0.5 to 5 Rg/m skin loadings, field use would be very limited by the size and transportability of the instrument and the liquid-nitrogen coolant for the detector. Whatever the method, surface residues are also difficult to measure quantitatively in situ, especially on the skin. 

Attenuated Total Reflectance This method can be used to identify solid drugs but is only of use where relatively large amounts of compounds are available. The finely-ground sample is spread as a thin layer onto the sticky side of a piece of self-adhesive tape, and the tape is placed against the reflecting surface of the instrument with the sample side in contact. Sufficient sample is required to cover the surface of the tape completely, otherwise the spectrum of the tape will be recorded in addition to that of the sample. The technique is of use when the acid and salt forms need to be differentiated. 

Important to quality control are the comparison and confirmation of drug substance identity, excipients, and packaging components. Techniques such as Fourier transform IR (FTIR), attenuated total reflectance (ATR), NIR, Raman spectroscopy are used with increased regularity. The detection of foreign metal contaminants is essential with inductively coupled plasma spectroscopy (ICP), atomic absorption (AA), and X-ray fluorescence. Also notable is the increased attention to analysis of chiral compounds, as in the synthesis of drug substances. Optical rotation, ORD, and CD are currently the preferred instruments for this practice. The analytical techniques commonly used in the preformulation study are discussed in the following. 

Double beam spectrophotometers allow differential measurements to be made between the sample and the analytical blank. They are preferable to the single beam instruments for cloudy solutions. The bandwidth of high performance instruments can be as small as 0.01 nm. For routine measurements such as monitoring a compound on a production line, an immersion probe is employed. Placed in the sample compartment of the apparatus this accessory contains two fibre-optics, one to conduct the light to the sample and another to recover it after absorption in the media studied. Two types exist by transmission for clear solutions and by attenuated total reflection (ATR) for very absorbent solutions (Figure 9.17). 

The FTIR spectra were recorded with a Nexus instrument (Nicolet, USA) using the ATR (attenuated total reflectance, 45° angle of incidence) technique with a diamond or a Ge cell ( Golden Gate, Specac, Kent, UK). The IR signal comes from a near-surface layer of the polymer film. The information depth de-... 

The evolution of instrumentation in IR spectroscopy bears a similarity to that of NMR in that modem spectrometers collect data differently from the methods used by older instmments and convert it to a spectmm by Fourier transform (FT) methods. The present generation of IR spectrometers employs a technique known as attenuated total reflectance (ATR) coupled with FT data analysis. The whole range of vibrational states is sampled at once and transformed by Fourier analysis to give a spectmm formatted in the custom of traditional instmments. Recording an FT-IR spectmm takes about 1 min, compared with the 10-15 min needed for older instmments. 

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