Process spectroscopy, analytical method

The objective ia any analytical procedure is to determine the composition of the sample (speciation) and the amounts of different species present (quantification). Spectroscopic techniques can both identify and quantify ia a single measurement. A wide range of compounds can be detected with high specificity, even ia multicomponent mixtures. Many spectroscopic methods are noninvasive, involving no sample collection, pretreatment, or contamination (see Nondestructive evaluation). Because only optical access to the sample is needed, instmments can be remotely situated for environmental and process monitoring (see Analytical METHODS Process control). Spectroscopy provides rapid real-time results, and is easily adaptable to continuous long-term monitoring. Spectra also carry information on sample conditions such as temperature and pressure. 

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 seven 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... 

Above mentioned examples clearly show that if multivariate data processing methods are applicable, analytical information can be derived with a minimal amount of pre-information and a foreseeing of a maximum of problems. When the sampled object is homogenous, multivariate methods are only applicable when the analytical method itself produces multivariate signals. This is the case when several signals (e.g. spectra) are obtained for the sample as a function of another variable (e.g. time, excitation wavelength). For e mple in GC-MS, a mass spectrum is m sured of the eluents every. 1 a 1 second. In excitation-emission spectroscopy, spectra are measured at several excitation-wavelengths. The potentials of the application of multivariate... 

Internal reflection spectroscopy is widely applied for on-line process control. In this type of application, the chemical reactor is equipped with an internal reflection probe or an IRE. The goal of this type of application is the quantification of reactant and/or product concentrations to provide real-time information about the conversion within the reactor. In comparison with other analytical methods such as gas chromatography, high-pressure liquid chromatography, mass spectrometry, and NMR spectroscopy, ATR spectroscopy is considerably faster and does not require withdrawal of sample, which can be detrimental for monitoring of labile compounds and for some other applications. 

The analytical method for moisture determination must be validated before use during process validation studies. There are numerous techniques for moisture analysis that range from physical methods, such as loss on drying, to chemical methods, such as Karl Fisher titration. A comparative review of the conventional techniques are presented in an overview [32], The measurement of residual moisture is lyophilized pharmaceuticals by near-infrared (NIR) spectroscopy has recently been expanded [33]. 

It was mentioned earlier that empirical multivariate modeling often requires a very large amount of data. These data can contain a very large number of samples (N), a very large number of variables (M), or both. In the case of PAC, where the analytical method is often a form of spectroscopy or chromatography, the number of variables collected per process sample can range from the hundreds to the thousands ... 

---