Ultraviolet/visible spectroscopy precision

Recently, ICH guidance Q6A has simplified the development of specifications in several ways, not the least of which is the clarification that impurities if already controlled in the API do not have to be controlled in the dosage form unless they are also degradants. For the release assay, this paves the way for simpler, but no less sophisticated methods that require minimal sample preparation. Thus, the future may bring a return to spectroscopic techniques such as ultraviolet/visible (LJV/vis) spectroscopy. There also may be increased use of other high-speed and high-precision techniques such as flow injection analysis (FIA) and near infrared (NIR) analysis. 

Until the early 1980s, most mid-IR spectrometer systems were double-beam dispersive grating spectrometers, similar in operation to the double-beam system for ultraviolet/visible (UV/VIS) spectroscopy described in Chapter 2. These instruments have been replaced almost entirely by FTIR spectrometers because of the advantages in speed, signal-to-noise ratio, and precision in determining spectral frequency that can be obtained from a modem multiplex instrument. There are NIR instruments that are part of double-beam dispersive UWVIS/NIR systems, but many NIR instruments are stand-alone grating instruments. 

Various kinds of visible and ultraviolet spectroscopy—absorption, excitation, emission—are well suited for monitoring certain reaction intermediates. These techniques are complementary to X-ray in that they provide excellent sensitivity and time resolution but low structural precision. 

Precision measurement of energy intervals in hydrogen and helium has been fundamental to the development of atomic theory. Relativistic and quantum-electrodynamic contributions scale with various powers of Z. Hence more information is gained by extending precise measurements to one- and two-electron ions. Laser spectroscopy is restricted to certain special transitions which fall in the infrared, visible or near-ultraviolet, and from which a useful signal can be obtained. However, where applicable, it provides precision tests of theory. The focus of this review is laser spectroscopy of the n = 2 levels of moderate-Z helium-like and hydrogen-like ions. Previous reviews may be found in [1,2,3],... 

Infrared spectroscopy is a less satisfactory tool for quantitative analyses than its ultraviolet and visible counterparts because of lower sensitivity and frequent deviations from Beer s law. Additionally, infrared absorbance measurements are considerably less precise. Nevertheless, in instances where modest precision is adequate, the unique nature of infrared spectra provides a degree of selectivity in a quantitative measurement that may offset these undesirable characteristics. ... 

Historically important in the development of modern atomic theory was the recognition that although polyatomic molecules show more or less broad bands of absorption and emission in the visible and ultraviolet regions of the spectrum, the characteristic light absorption or emission by individual atoms occurs at fairly narrow lines of the spectrum, which correspond to sharply defined wavelengths. The line spectrum of each element is so uniquely characteristic of that element that atomic spectroscopy can be used for precise elementary analysis of many types of chemically complex materials. 

Noble gases are intrinsically difficult to detect by spectroscopy. For example, solar photospheric spectra, which form the basis for solar abundance values of most elements, do not contain lines from noble gases (except for He, but this line cannot be used for abundance determinations). Yet, ultraviolet spectroscopy is the only or the major source of information on noble gas abundances in the atmospheres of Mercury and comets. In the Extreme Ultraviolet (EUV), photon energies exceed bond energies of molecules and the first ionization potential of all elements except F, He, and Ne, so that only these elements are visible in this part of the spectrum (Krasnopolsky et al. 1997). Other techniques can be used to determine the abundance of He where this element is a major constituent. Studies of solar oscillations (helioseismology) allow a precise determination of the He abundance in the solar interior, and the interferometer on the Galileo probe yielded a precise value for the refractive index and hence the He abundance in the upper atmosphere of Jupiter (see respective sections of this chapter). 

This article provides some general remarks on detection requirements for FIA and related techniques and outlines the basic features of the most commonly used detection principles, including optical methods (namely, ultraviolet (UV)-visible spectrophotometry, spectrofluorimetry, chemiluminescence (CL), infrared (IR) spectroscopy, and atomic absorption/emission spectrometry) and electrochemical techniques such as potentiometry, amperometry, voltammetry, and stripping analysis methods. Very few flowing stream applications involve other detection techniques. In this respect, measurement of physical properties such as the refractive index, surface tension, and optical rotation, as well as the a-, //-, or y-emission of radionuclides, should be underlined. Piezoelectric quartz crystal detectors, thermal lens spectroscopy, photoacoustic spectroscopy, surface-enhanced Raman spectroscopy, and conductometric detection have also been coupled to flow systems, with notable advantages in terms of automation, precision, and sampling rate in comparison with the manual counterparts. 

The ordering of probe molecules in liquid crystals was in fact known much earlier than 1968. It is widely used to determine various parameters of the solute and solvent liquid crystal using nuclear magnetic resonance (NMR), electron spin resonance (ESR), ultraviolet (UV), visible, and other spectroscopie teehniques. After the pioneering work of Saupe and Englert in 1963 [8], the NMR spectroscopy of molecules oriented in liquid crystals became very important in structural chemistry, as it provides the only direct method for precise determination of the molecular geometries in liquid phase. In addition to structural and confor-... 

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