Drug purity analysis

The use of UV-vis and FT-IR spectroscopy in determining drug impurities without previous chromatographic separation is limited because of the low selectivity of both methods. In some cases, when the impurity has spectral properties that are very different from those of the active substance, the direct measurement of absorbance can give some useful data about the structure of the impurity. But, in many cases the impurity has a similar structure to the active substance and, therefore, their UV and IR absorption spectra are similar, and overlap with each other additively. This means that direct use of spectroscopic methods in drug purity analysis is limited [49]. 

Selectivity of the UV method can be increased by the use of spectra derivatives [50]. Derivative spectrophotometry is a chemometric method in which classic UV spectra (zero-order spectra) are differentiated with respect to wavelength before being analyzed. It is much more selective and precise than classic UV spectroscopy [50]. Examples of the use of the spectra derivatives method in drug purity analysis are shown in Table 8.4. 

In drug purity analysis when several (closely related) compounds have to be separated, the methods have to be optimized with regard to multiple criteria, including the resolution between analytes that react sensitively to changes of the experimental conditions (so-called critical pairs) and/or analysis time. Sometimes, multiple critical pairs exist. Thus, experimental design... 

P. F. Vanbel, J. A. Gilliard, and B. Tiliquin, Chemometric optimization in drug analysis by HPLC a critical evaluation of the quality criteria used in the analysis of drug purity, Chromatographia, 36 120 (1993). 

An important fact inherent in the purity analysis of a recombinant pharmaceutical is that the absolute purity of any protein is an elusive, if not an unobtainable, measurement. For biopharmaceuticals, purity is a relative term. Protein purity is method-dependent and is defined by the shortcomings of the analytical procedure. Also, unlike small traditional drugs, proteins are highly complex molecules. For these two reasons, more than one method must be utilized to define a protein s purity. The greater the number of methods used in the purity analysis, the greater the assurance is that the product is pure. Furthermore, the purity determined by an analytical method can only be properly interpreted based on the method s validation. Analytical methods validation is critical to and inseparable from purity determinations. A detailed discussion on analytical methods validation is beyond the scope of this chapter but other sources of information are available for the interested reader.11 13... 

A manufacturer may use his own standard instead of an official standard but in this case there are requirements that have to be met such as the submission of the details of the standard and method of analysis used. The standard must meet two criteria it must ensure the highest degree of drug purity and the least variation on potency. 

See also Capillary Electrophoresis Overview Clinical Applications. Pharmaceutical Analysis Overview Drug Purity Determination. 

See also Chemometrics and Statistics Statistical Techniques Multivariate Classification Techniques Multivariate Calibration Techniques. Food and Nutritional Analysis Overview. Fourier Transform Techniques. Fuels Oil-Based. Infrared Spectroscopy Overview. Pharmaceutical Analysis Drug Purity Determination. Process Analysis Ovenriew. Proteins Foods. Quality Assurance Ouality Control. Textiles Natural Synthetic. 

See also Paints Water-Based. Pharmaceutical Analysis Drug Purity Determination. 

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