Identification of pharmaceuticals

A. Candolfi, R. De Maesschalk, D.L. Massart, P.A. Hailey and A.C.E. Harrington, Identification of pharmaceutical excipients using NIR spectroscopy and SIMCA. J. Pharm. Biomed. Anal., in prep. 

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... 

The analysis of pharmaceutical agents in preparations has been one of the most important applications of modem RPC. A simple gradient maker to be used on the low pressure side of the pump for use in gradient elution of pharmaceuticals has been described (560). For the detection and identification of pharmaceuticals, micro internal reflection infrared spectroscopy (561) and ultraviolet scanning spectroscopy with stopped flow (562) were also employed. 

Table 10.1 lists selected references to the identification of pharmaceutical raw materials. As can be seen, a variety of techniques have been used, which fall short of the discriminating power of the previous ones and have not yet been included by manufacturers in their equipment software. This makes them inconvenient to implement. 

A second approach to determining optimum TLC systems is based on principal components analysis. This is another statistical approach aimed at the identification of pharmaceuticals [76]. By using this approach on 360 drugs, 4 mobile phases from a set of 40 were chosen as giving the most diverse chromatographic information. Table 3.7 lists the four chosen mobile phases. 

P. Balatre and M. Traisnel, Identification of pharmaceutical dyes by thin-layer chromatography of their complexes with a quaternary ammonium compound, Bull. Trav. Soc. Pharm. Lyon, 9 41 (1965). 

M. E. Swartz and P. R. Brown, Use of mathematically enhanced spectral analysis and spectral contrast techniques for the liquid chromatographic and capially electrophoretic detection and identification of pharmaceutical compounds. Chirality 8 (1996), 67-76. 

Identification of pharmaceutically acceptable vehicles that afford sufficient solubilization while maximizing physiological compatibility for preclinical pharmacokinetic evaluation is critical. The most frequently used solubilization techniques include pH manipulation for ionizable compounds use of cosolvents such as PEG 400, ethanol, DMSO, and propylene glycol micellar solubilization with surfactants such as Tween 80 or SLS complexation with cylodextrins [40]. By using the solubilization techniques, the enhancement in solubility of poor water-soluble compounds can be significant compared to aqueous solubility and can facilitate the absorption of drug molecules in the gastrointestinal tract when delivered in solution form. 

Table 4 Compendial applications of GC for the identification of pharmaceutical raw materials and dosage forms... 

Eiceman et al. demonstrated that IMS can be used to verily the content of some common over-the-counter pharmaceuticals. The tablet or capsule was slightly warmed, and headspace vapors were sampled by a handheld IMS mobility spectra were compared with known spectra to confirm the prescription. As mentioned, the application of IMS for detection and identification of pharmaceuticals, as opposed to illicit drugs, is discussed in Chapter 15. 

Holman SW, Wright P, Langley GJ. High-throughput approaches towards the definitive identification of pharmaceutical drug metabolites. 2. An example of how unexpected dissociation behaviour could preclude correct assignment of sites of metabolism. Rapid Commun Mass Spectrom 2009 23 2017-2025. 

NIR-Raman has found applications in the pharmaceutical industry. McCreery and colleagues reported the use of the technique for identification of pharmaceuticals inside amber vials. Even with the signal attenuation through the glass, adequate spectra were obtained for determination of vial content with 1-60 s integration times. Using a library of spectra, identification of the pharmaceuticals in the vials was performed and identification was found to display accuracy between 88% and 96%. This work demonstrated the potential of NIR-Raman for online process monitoring. 

Retrospective analysis to search for compounds not included in the initial analysis is an attractive feature of TOP MS-based methods. Without additional injection of the samples, it is feasible to investigate the presence of other contaminants or metabolites. This has allowed the detection and identification of pharmaceutical metabolites in wastewater [51]. Obviously, this possibility is also available to other compounds, pesticides included, provided that they are compatible with the sample treatment and LC—MS analysis applied. A detailed comparison of the capabilities of LC—MS using QqQ, TOP, and QTOP for quantification, confirmation, and screening in the field of PRA is given in [45]. 

In this book, we only give some examples of recommended identifications of pharmaceutical products through measurements of melting points. There are two possibilities either the measured melting point is that of the substance to be identified or it is that of one of its immediate derivatives. The second possibility is the more frequent one. We ll mention the identifications of... 

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