Quantitation of impurities

An example of release testing by TLC is shown in Fig. 13.24. In this example, two more polar bands are observed, one that is quantitated at <0.1% and another at 0.3%. Quantitations are based on visual estimation using the standards on the plate. Alternatively, scanning densitometry can be utilized to obtain a more definitive quantitation of impurities. 

ELISAs can be used for identification and quantitation of a biopharmaceutical product or for quantitation of impurities or contaminants as discussed previously. They can be used throughout the manufacturing process as well as in quality control or the product release stage just as they are used in all the other stages of product development. To be used for quality control, GMP practices must be followed. All methods need to be validated so that the assay s performance is documented. ELISAs should have internal quality controls to monitor assay... 

Inappropriate response factors may have been used for quantitation of impurities/degradation products (i.e., molar extinction coefficients of degradation products are less than those of the API). 

E. Bertol, F. Mari, and M. G. Di Milia, Programmable temperature vaporizer applications in an high-resolution gas chromatographic method for the quantitation of impurities in illicit heroin, J. Chromatogr., 466 384(1989). 

G. Chevalier, P. Rohrbach, C. Bollet, and M. Caude, Identification and quantitation of impurities from benorilate by HPLC, J. Chromatogr., 735 193 (1977). 

Purity determination is an essential component of the assessment of the quality of any drug. However, the purity determination of biopharmaceuticals is not as straightforward as for small-molecule pharmaceuticals because biopharmaceuticals are structurally complex and have a wide range of potential impurities. Approaches usually involve the judicious choice of a combination of methods that will enable the detection and quantitation of impurities from which an overall purity assessment can be made. CE-generated data now play a significant role in such purity assessments. 

V. REFERENCE STANDARDS FORTHE QUANTITATION OF IMPURITIES AND ANALYTICAL PROCEDURES... 

There are also an increasing numbers of analyses that make use of NMR quantitative, either for limit tests, quantitation of impurities or for assays of components in dmg substance or dmg product. Section 4.4 discusses the requirements for quantitative NMR and the practical aspects, including validation of NMR methods. 

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