Difference Raman spectroscopy spectrometer

The use of vibrational Raman spectroscopy in qualitative analysis has increased greatly since the introduction of lasers, which have replaced mercury arcs as monochromatic sources. Although a laser Raman spectrometer is more expensive than a typical infrared spectrometer used for qualitative analysis, it does have the advantage that low- and high-wavenumber vibrations can be observed with equal ease whereas in the infrared a different, far-infrared, spectrometer may be required for observations below about 400 cm. ... 

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. 

Owing to the very high rate of decomposition, in-situ measurement of concentration by means of Raman spectroscopy was applied. The peroxide used was f-butylperoxy pivalate (see Chapter 5.1, Table 5.1-2) dissolved in n-heptane at a concentration of 1 wt.%. In order to observe the change in intensity of absorption of the 0-0 bond at 861 cm 1, the spectrometer was adjusted to this wave number. The change of intensity is an indication of the reduction in the peroxide concentration, and was recorded as a function of time. The apparatus was calibrated before measuring the intensity of peroxide solutions of different concentrations [22],... 

Active pharmaceutical ingredients (API) can be identified using many different analytical approaches. A Raman spectroscopy method may not be the most common or economical but it does offer significant advantages. These include rapid, sensitive analysis, information-rich spectra, minimal or no sampling [32]. Handheld Raman spectrometers now allow the measurement to be taken to samples allowing analysis at the point of receipt and not just in a... 

Raman spectroscopy has developed rapidly in the past few years and there are very interesting prospects for future process applications. By building on the fact that Raman spectroscopy is fast, selective, informative and can be remotely coupled to process vessels, it is very likely that we will see Raman spectrometers much more widely used in pharmaceutical manufacturing. Several challenges are still hampering future success in some areas as discussed above. In particular, more efforts on interfacing the Raman spectrometer to different secondary process unit operations are needed before we will see the robust use of the technique. 

The classical Raman effect produces only very weak signals. There are two techniques which very successfully enhance this effect. The resonance Raman spectroscopy RRS is making use of the excitation of molecules in a spectral range of electronic absorption. The surface-enhanced Raman spectroscopy SERS employs the influence of small metal particles on the elementary process of Raman scattering. These two techniques may even be combined surface-enhanced resonance Raman effect SERRS. Such spectra are recorded with the same spectrometers as classical Raman spectra, although different conditions of the excitation and special sample techniques are used (Sec. 6.1). 

Delhaye and Dhamelincourt (1975) were the first to combine a Raman spectrometer with a microscope. Kiefer (1988) described the Raman spectroscopy of single particles of aerosols by the optical levitation technique, an approach which is even possible with a compact spectrometer (Hoffmann et al., 1992). Raman spectra recorded with NIR FT Raman microscopes have proven the value of this technique (Messerschmidt and Chase, 1989 Bergin and Shurwell, 1989 Simon and Sawatzki, 1991). Examples of micro Raman spectra obtained from different spots on certain biological samples have been published (Schrader, 1990 Puppels et al., 1991). 

Raman spectroscopy requires highly monochromatic light, which can be provided only by a laser source. The laser source is commonly a continuous-wave laser, not a pulsed laser. The laser source generates laser beams with the wavelengths in the visible light range or close to the range. In a Raman microscope, sample illumination and collection are accomplished in the microscope. The microscope s optical system enables us to obtain a Raman spectrum from a microscopic area this is the main difference between the micro-Raman and conventional Raman spectrometers. 

These FT-Raman and CCD-Raman spectrometers revolutionized Raman spectroscopy such that, within the space of about five years, about ten different Raman spectrometers based on multiplex and multicharmel technologies had been introduced commercially [32, 33]. Several of the CCD-Raman spectrometers were either designed for, or could be readily modified for, microspectroscopy. Although FT-Raman microspectrometers have been reported (e.g.. Ref [34]), they have not proved very popular for three reasons ... 

The molecular structures of the surface vanadium oxide species on the different supports were examined with Raman spectroscopy. The Raman spectrometer system possessed a Spectra-Physics Ar+ laser (model 2020-05) tuned to the exciting line at 514.5 nm. The radiation intensity at the samples was varied from 10 to 70 mW. The scattered radiation was passed through a Spex Triplemate spectrometer (Model 1877) coupled to a Princeton Applied Research OMA III optical multichannel analyzer (Model 1463) with an intensified photo diode array cooled to 233 K. Slit widths ranged from 60 to 550 m. The overall resolution was better than 2 cm l. For the in situ Raman spectra of dehydrated samples, a pressed wafer was placed into a stationary sample holder that was installed in an in situ cell. Spectra were recorded in flowing oxygen at room temperature after the samples were dehydrated in flowing oxygen at 573 K. 

In order to implement Raman spectroscopy, a reference sample is firstly installed in the sample chamber in moveable cuvette. Sulfur is usually used as the reference sample because of its high Raman activity. The reference sample is moved in the sample chamber until an optimum position is found. The optimum position is marked by maximum scattered radiation recorded by the detector. After the optimum position has been found, the reference sample is replaced with actual, sample. It is important to note that the geometrical characteristics of the actual sample must be the same as those of the reference sample. Calibration with regard to wavelength of the light used for the analysis depends on the actual sample and Raman spectrometer used. Different methods can be found in handbooks for a given Raman spectrometer. 

Spectroscopic methods can provide fast, non-destructive analytical measurements that can replace conventional analytical methods in many cases. The non-destructive nature of optical measurements makes them very attractive for stability testing. In the future, spectroscopic methods will be increasingly used for pharmaceutical stability analysis. This chapter will focus on quantitative analysis of pharmaceutical products. The second section of the chapter will provide an overview of basic vibrational spectroscopy and modern spectroscopic technology. The third section of this chapter is an introduction to multivariate analysis (MVA) and chemometrics. MVA is essential for the quantitative analysis of NIR and in many cases Raman spectral data. Growth in MVA has been aided by the availability of high quality software and powerful personal computers. Section 11.4 is a review of the qualification of NIR and Raman spectrometers. The criteria for NIR and Raman equipment qualification are described in USP chapters <1119> and < 1120>. The relevant highlights of the new USP chapter on analytical instrument qualification <1058> are also covered. Section 11.5 is a discussion of method validation for quantitative analytical methods based on multivariate statistics. Based on the USP chapter for NIR <1119>, the discussion of method validation for chemometric-based methods is also appropriate for Raman spectroscopy. The criteria for these MVA-based methods are the same as traditional analytical methods accuracy, precision, linearity, specificity, and robustness however, the ways they are described and evaluated can be different. 

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