Discriminant analysis, pharmaceutical

Ciurczak, E. W. Use of near infrared for discriminate analysis of pharmaceutical raw materials. 

Figure 13.3-5. Partial least-squares discriminant analysis model for the classification of blood plasma samples in terms of coronary artery disease, based on their NMR spectra with visualization of the degree of coronary artery occlusion. Each point is based on data from a NMR spectrum of human blood plasma from subjects with different degrees of coronary artery occlusion. Circles—no stenosis, triangles—stenosis of one artery, inverted triangles—stenosis of two arteries, and squares—stenosis of three arteries. (This figure is available in full color at ftp //ftp.wiley.com/public/sci tech med/pharmaceutical biotech/.)...

Discriminant analysis of NIR spectra was used in 1986 to assay the level of lincomycin in a pharmaceutical formulation. This was the first NIR analysis to be accepted by this US Food and Drug Administration (FDA). NIR is now used to measure the salicylic acid content of aspirin and pharmaceutical companies use discriminant NIR procedures to check incoming raw materials for drug production. Sample identification can be achieved using at-line NIR fiber optic systems. 

P. P. Sanghvi, J. K. Drennen, and C. C. Collins, Discriminant Analysis of Pharmaceutical Components Using NIRA, presented at AAPS Annual Meeting, San Diego, CA, November 1994, paper PT 6058. 

In 1984, Mark introduced the Mahalanobis distance in an algorithm for discriminant analysis of raw materials. The theory behind the software was described in a paper by Mark and Turmell [21] and first applied to pharmaceuticals by Ciurczak [22]. With the advent of 100% testing of incoming raw materials, qualitative analysis of raw materials by NIR became popular quickly. 

E.L. Izaki, Enantioselective discrimination analysis of chiral drugs An overview. Journal of Pharmaceutical Sciences, 96 (7), 1659-1676,2007. 

Wet granulation and direct compression are two methods used to manufacture tablets in the pharmaceutical industry. Zomer et al. used pyrolysis-gas chromatography-mass-spectrometry coupled with SVM classification to discriminate between the two tablet production methods.Mass spectra data were submitted to a PCA analysis, and the first principal components were used as input for SVM models having linear, polynomial, and Gaussian RBF kernels. SVM classifiers with polynomial and RBF kernels performed better in prediction than discriminant analysis. 

The context of this work, at least superficially, is quality control in the chemical and pharmaceutical industries. The general principles apply to any form of (chemical) analysis, however, whether in an industrial setting or not. Other readers need only to replace some phrases, such as Health Authority with discriminating customer or official requirements with market expectations, to bridge the gap. The specifically chemical or pharmaceutical nomenclature is either explained or then sufficiently circumscribed so that the essentials can be understood by students of other disciplines. 

Unlike, e.g. in pharmaceutical metabolism studies, where the parent compound is known and thus some preliminary knowledge of the expected structures is available, the composition of a natural products extract is often completely unknown beforehand ( non-target analysis ). In such cases, NMR spectroscopy is especially well suited as a detection system since it does not discriminate any classes of compounds. (Sufficient relaxation delays provided, the NMR signal depends only on the number of nuclei in the active probe volume.)... 

Discrimination among all of these is a trivial exercise. Both B vitamins and C were easily quantitated in prepared mixtures as expected [59], but it was also relatively easy to measure each one after its simple extraction into aqueous buffer from pharmaceutical preparations, as well as (in the case of vitamin C) from extracts of fruit, fruit juices, and vegetables. A very thorough inventory of tests for possible interferences was run and the resultant analytical data for the vitamins compared extremely well with the labelled contents on the packages of pharmaceutical products and with the data in compendia that list the average compositions of vitamins and other essential products in plant food materials [33]. Analysis of the major fat soluble D2 and D3 vitamins (ergocalciferol and cholecalciferol) has not progressed with the... 

Flavors are widely used in pharmaceutical solutions to mask drug bitterness. Zhu s group [48] has used an MOS electronic nose to perform headspace analysis of these formulations. The method was able to qualitatively distinguish six common flavors (raspberry, red berry, strawberry, pineapple, orange, and cherry) in placebo mixtures. The instrument was also able to identify unknown flavors. It was also indicated that the instrument could be used to identify different flavor raw materials. Moreover, the electronic nose was used for quantitative analysis of flavors in an oral solution. Data processing and identification were done by PCA, discriminant factorial analysis (DFA), and partial least squares. 

Just as modem liquid chromatography (LC) is the dominant separative technique in the analysis of pharmaceuticals, so, in the evolution of methodologies for the chiral analysis of pharmaceuticals, LC has emerged as the pre-eminent technique. As already intimated, discrimination between enantiomers requires the presence of a chiral selector. In the determination of enantiomers by LC... 

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