Quantitative analysis Raman spectroscopy

The IR spectra of all four crystal modifications were reported by Cady and Smith (1962) and by Holston (1962). The latter did point out some distinguishing features among the polymorphs, but Cady and Smith noted that problems with sample preparation and conversions among forms indicated that the optical properties described by McCrone (1950a) were the basis for the best rapid qualitative and even rough quantitative analysis. Raman spectroscopy, which requires less potentially destructive sample preparation, has been used to distinguish the polymorphs (Goetz and Brill 1979). The low resolution NMR spectra of the four crystal modifications were reported by Landers et al. (1985). The nuclear quadrupole resonance spectrum... 

Principles and Characteristics Raman spectroscopy is mainly utilised as a qualitative tool, but can also be employed quantitatively [191]. Quantitative analysis by Raman spectroscopy has not kept pace with the rapid growth in the use of Raman spectroscopy for stmctural and qualitative analysis. Quantitative FT-Raman spectroscopy can be made as routine and reliable as absorption spectroscopy [192,193]. 

Examples that use Raman spectroscopy in the quantitative analysis of materials are enonnous. Technology that takes Raman based techniques outside the basic research laboratory has made these spectroscopies also available to industry and engineering. It is not possible here to recite even a small portion of applications. Instead we simply sketch one specific example. 

Failloux, N, Bonnet, I, Baron, MH, and Perrier, E, 2003. Quantitative analysis of vitamin A degradation by Raman spectroscopy. Appl Spectrosc 57, 1117-1122. 

Most chemists tend to think of infrared (IR) spectroscopy as the only form of vibrational analysis for a molecular entity. In this framework, IR is typically used as an identification assay for various intermediates and final bulk drug products, and also as a quantitative technique for solution-phase studies. Full vibrational analysis of a molecule must also include Raman spectroscopy. Although IR and Raman spectroscopy are complementary techniques, widespread use of the Raman technique in pharmaceutical investigations has been limited. Before the advent of Fourier transform techniques and lasers, experimental difficulties limited the use of Raman spectroscopy. Over the last 20 years a renaissance of the Raman technique has been seen, however, due mainly to instrumentation development. 

An important tool for the fast characterization of intermediates and products in solution-phase synthesis are vibrational spectroscopic techniques such as Fourier transform infrared (FTIR) or Raman spectroscopy. These concepts have also been successfully applied to solid-phase organic chemistry. A single bead often suffices to acquire vibrational spectra that allow for qualitative and quantitative analysis of reaction products,3 reaction kinetics,4 or for decoding combinatorial libraries.5... 

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. 

Dramatic improvements in instrumentation (lasers, detectors, optics, computers, and so on) have during recent years raised the Raman spectroscopy technique to a level where it can be used for species specific quantitative chemical analysis. Although not as sensitive as, for example IR absorption, the Raman technique has the advantage that it can directly measure samples inside ampoules and other kinds of closed vials because of the transparency of many window materials. Furthermore, with the use of polarization techniques, one can derive molecular information that cannot be obtained from IR spectra. Good starting references dealing with Raman spectroscopy instruments and lasers are perhaps [34-38]. 

Finally, Raman spectroscopy has a potential of being used for qualitative and quantitative analysis. We have used Raman spectroscopy to verify the presence of components in a two-phase system [29]. 

Raman spectroscopy is a related vibrational spectroscopic method. It has a different mechanism and therefore can provide complementary information to infrared absorption for the peptide protein conformational structure determination and some multicomponent qualitative and/or quantitative analysis (Alix et al. 1985). 

Inductively Coupled and Microwave Induced Plasma Sources for Mass Spectrometry 4 Industrial Analysis with Vibrational Spectroscopy 5 Ionization Methods in Organic Mass Spectrometry 6 Quantitative Millimetre Wavelength Spectrometry 7 Glow Discharge Optical Emission Spectroscopy A Practical Guide 8 Chemometrics in Analytical Spectroscopy, 2nd Edition 9 Raman Spectroscopy in Archaeology and Art History 10 Basic Chemometric Techniques in Atomic Spectroscopy... 

For formulated products an essential analysis is the assay for API content. This is usually performed by HPLC, but Raman spectroscopy can offer a quantitative analytical alternative. These applications have been extensively researched and reviewed by Strachan et al. [48] and provide over 30 literature references of where Raman spectroscopy has been used to determine the chemical content and physical form of API in solid dosage formulations. As no sample preparation is required the determination of multiple API forms (e.g. polymorphs, hydrates/solvates and amorphous content) provides a solid state analysis that is not possible by HPLC. However, as previously discussed sampling strategies must be employed to ensure the Raman measurement is representative of the whole sample. A potential solution is to sample the whole of a solid dosage form and not multiple regions of it. As presented in Chap. 3 the emerging technique of transmission Raman provides a method to do just this. With acquisition times in the order of seconds, this approach offers an alternative to HPLC and NIR analyses and is also applicable to tablet and capsule analysis in a PAT environment. 

NIR, Raman would be expected to offer advantages such as ease of use for quantitative analysis. The reason for less widespread use of process Raman spectroscopy is due in part to more expensive equipment, relative to NIR. A broader implementation of process Raman spectroscopy in the pharmaceutical industry has previously also been hampered by inherent weaknesses in sampling in remote measurements on solids. This is discussed further in Section 10.3. 

For a quantitative analysis or classification of biological or medical problems by means of Raman spectroscopy the application of multivariate spectral analysis methods is required. These multivariate methods allow one to extract diagnostic, chemical, and morphological relevant information out of the complex Raman spectrum and must be applied due to the high amount of similar spectral features. 

Pelletier, M.J. Quantitative Analysis Using Raman Spectroscopy Appl. Spectrosc. 2003,57,20A-42A. 

Ryder, A.G., O Connor, G.M. and Glynn, T.J. (1999) Identifications and quantitative measurements of narcotics in solid mixtures using near-IR Raman spectroscopy and multivariate analysis /. Forensic Sci. 44, 1013-1019. 

Rohleder D, Kiefer W, Petrich W. Quantitative analysis of serum and serum ultrafiltrate by means of Raman spectroscopy. Analyst 2004, 129, 906-911. 

A limiting factor in noninvasive optical technology is variations in the optical properties of samples under investigation that result in spectral distortions44 8 and sampling volume (effective optical path length) variability 49-54 These variations will impact a noninvasive optical technique not only in interpretation of spectral features, but also in the construction and application of a multivariate calibration model if such variations are not accounted for. As a result, correction methods need to be developed and applied before further quantitative analysis. For Raman spectroscopy, relatively few correction methods appear in the literature, and most of them are not readily applicable to biological tissue.55-59... 

The same general principle that applies for intrinsic fluorescence should hold true for Raman spectroscopy as well. Unlike in fluorescence spectroscopy, spectral distortion owing to prominent absorbers is less of an issue in the NIR wavelength range. However, for quantitative analysis the turbidity-induced sampling volume variations become very significant and usually dominate over spectral distortions. 

Concentration profiting uses on- or in-line measurements of optical properties, typically not done for the whole volume, but along lines such as the channel cross-section (see e.g. [20]). Concentrations are accessible by photometric, electric or fluorescence measurements. Furthermore, vibrational analysis such as IR and Raman spectroscopy can be used for the same task [80,81]. Concentration profiling can also be achieved simply by gray-scale or comparable image analysis for quantitative data extraction from microscopy images of colored flows [20, 37, 68],... 

Another quantitative spectroscopic technique for the analysis of additives in lubricants and hydrocarbons is Raman spectroscopy (Coates, 1975). Theoretically, Raman spectroscopy should be as good as infrared for quantitative analysis. The... 

---