Quantitative Raman

Quantitative Raman spectroscopy is an established technique used in a variety of industries and on many different sample forms from raw materials to in-process solutions to waste streams, including most of the applications presented here [1]. Most of the applications presented in the next section rely on quantitative analysis. Similar to other spectroscopic techniques, many factors influence the accuracy and precision of quantitative Raman measurements, but high quality spectra from representative samples are most important. 

Raman often is evaluated as an alternative to an existing high performance liquid chromatography (HPLC) method because of its potential to be noninvasive, fast, simple to perform, and solvent-free. Raman was compared to HPLC for the determination of ticlopidine-hydrochloride (TCL) [43], risperidone [44] in film-coated tablets, and medroxyprogesterone acetate (MPA) in 150-mg/mL suspensions (DepoProvera, Pfizer) [45] it was found to have numerous advantages and performance suitable to replace HPLC. In an off-line laboratory study, the relative standard deviation of the measurement of the composition of powder mixtures of two sulfonamides, sulfathiazole and sulfanilamide, was reduced from 10-20% to less than 4% by employing a reusable, easily prepared rotating sample cell [46]. 

Since a larger sample volume is presumed to be probed, the use of transmission mode has led to simpler, more accurate models requiring fewer calibration samples [50]. Scientists at AstraZeneca found that with a transmission Raman approach as few as three calibration samples were required to obtain prediction errors nearly equivalent to their full model [42]. For a fixed 10-s acquisition time, the transmission system had prediction errors as much as 30% less than the WAI system, though both approaches had low errors. It is hoped that this approach in combination with advanced data analysis techniques, such as band target entropy minimization (BTEM) [51], might help improve Raman s quantitative sensitivity further. 

Major categories of process Raman applications include reaction monitoring, in-process quality checks, and mobile or field point measurements. Quality control laboratory applications often are converted to a continuous process monitoring approach, or could simply be viewed as part of a larger production process. 

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Ultrathin films of CdS ranging in coverage from 25 to 200 ML were grown also by the previous method on Au substrates (of non-specified nature) and were characterized by quantitative Raman resonance [41], It was found that the electronic structure of the films in this coverage regime corresponds to that of bulk CdS. It was concluded also that ECALE does not involve growth by random precipitation of CdS onto the Au surface the thin deposited layers of the material were contiguous. 

Raman spectroscopy is particularly well suited for use in process monitoring and conttol. This chapter discusses Raman spectroscopy s attractive features as well as alerts the reader to aspects that may present ehallenges. The fundamental principles of the technique are reviewed. The reader will learn about instrumentation and options in order to make the most appropriate choices. Special aspects of performing quantitative Raman spectroscopy are discussed since these are required in many installations. Apphcations from many diverse fields are presented. The reader is encouraged to examine aU of the areas since there are good lessons and stimulating ideas in aU. 

M.J. Pelletier, Quantitative Raman spectroscopy, Appl. Spectrosc., 57, 20A-42A (2003). 

P.J. Aamoutse and J.A. Westerhuis, Quantitative Raman reaction monitoring using the solvent as internal standard. Anal. Chem., 77, 1228-1236 (2005). 

Johansson, S. Pettersson and S. Folestad, Characterization of different laser irradiation methods for quantitative Raman tablet assessment, J. Pharm. Biomed. Anal., 39, 510-516 (2005). 

M. Kim, H. Chung, Y. Woo and M.S. Kemper, A new non-invasive, quantitative Raman technique for the determination of an active ingredient in pharmaceutical liquids by direct measurement through a plastic bottle. Anal. Chim. Acta, 587, 200-207 (2007). 

A. Picard, I. Daniel, G. Montagnac and P. Oger, In situ monitoring by quantitative Raman spectroscopy of alcoholic fermentation by Saccharomyces cerevisiae under high pressure, Extremophiles, 11, 445 52 (2007). 

Other sources of error, particularly in quantitative Raman analysis, include laser self-absorption effects leading to attenuation of some spectral bands. Similarly diffuse reflectance of the laser light, which is dependent on the particle size of the formulation components, may increase or decrease the collection volume. However, normalisation techniques can be used to overcome some of these effects [35]. 

O Sullivan discussed the influence of particle size on quantitative Raman monitoring in slurries [40], A system of P-form D-mannitol in toluene in the presence of sucrose was studied. It was found that although keeping the number and size of mannitol crystals constant the measured Raman signal varied with different particle size of the sucrose. These results show that particle size must always be taken into consideration in quantitative measurements and a linear relationship can not be taken for granted. 

Quantitative Raman Spectroscopy of Biomaterials for Arthroplastic Applications... 

Quantitative Raman Snect.roseonv of Riomat.eria.ls 411... 

Tinnemans SJ, Kox MHF, Nijhuis TA, Visser T, Weckhuysen BM. Real time quantitative Raman spectroscopy of supported metal oxide catalysts without the need of an internal standard. Physical Chemistry Chemical Physics 2005, 7, 211-216. 

The relatively new technique of quantitative Raman spectroscopy has been applied127 to the determination of the equilibrium constants for the reactions... 

Fig. 21. Content of crystalline MoOj derived from quantitative Raman study as a function of total content of M0O3 in the system Mo03/Ti02.

Quantitative Raman analysis The intensity of Raman band of an analyte is linearly proportional to the analyte concentration. A plot of analyte band area (integrated intensity) vs, analyte concentration is used to create an equation that predicts analyte concentration from Raman band area. This is an example of quantitative Raman analysis. 

In principle, one could calculate an absolute Raman cross section from the response of an instrument calibrated with a standard radiometric source. This approach is difficult but has been used to provide the cross sections in Table 2.2. If the relative response function is calibrated accurately, however, it is much simpler to determine cross sections by comparison to standards. Provided the sample positioning and optics permit quantitative Raman signal reproducibility, cross sections of liquids may be determined by comparing the response-corrected peak area to a band with known absolute cross section, such as the benzene 992 cm band. For response-corrected spectra, the ratio of the peak areas under identical experimental conditions equals the ratio of the absolute cross sections. 

The relatively recent technique of quantitative Raman spectroscopy has been applied to the determination of the equilibrium constants for the reactions in equation (2). The advantages of the technique include the direct proportionality of the signal obtained for a single complex species in a complicated equilibrium to the concentration of the species this is particularly advantageous in cases of mixed complex formation, where most methods give only indirect evidence for the existence of mixed species, and where very complicated relationships exist between measurable quantities and the total concentration of reactants. The results obtained (Xo-X3 = 5.3, 8.5, 5, 0.45) agree well with previous values obtained from polarographic and potentiometric studies. 

In contrast to NIR spectroscopy, the absolute values of the y-axis of a Raman measurement are difficult to quantify. Possible specific methods are described in USP chapter <1120> [21]. However, it is most common for quantitative Raman measurements to be done using the ratio of two peaks or other approaches which eliminate the need for absolute calibration of the y-axis. The USP chapter on Raman specifies that the photometric consistency or reproducibility specific integrated Raman band intensity should be on the order of 10%. 

The polybutadiene microstructures of a number of copolymers of butadiene and acrylonitrile were studied by quantitative Raman spectroscopy and a comparison was made with IR studies of these copolymers. The intensities of the v(C C) and the v(CN) bands were also used to determine the amount of each monomer in the copolymer. 24 refs. 

As far as the quantitative evaluation of vibrational spectra is concerned, MIR and NIR spectroscopy follow Beer s law, whereas the Raman intensity /Raman is directly proportional to the concentration of the compound to be determined (Figure 2.3). To avoid compensation problems, in most cases, quantitative Raman spectroscopy is performed with an internal reference signal in the vicinity of the analytical absorption band being analyzed. 

Qian W, Liu T, Wei F, Yuan H. Quantitative Raman characterization of the mixed samples of the single and multi-wall carbon nanotubes. Carbon 2003 41(9) 1851-1856. 

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