Purity determination and evaluation of new drug substances.
As a negative concept, purity is the absence of impurities and, hence, is not measurable directly. There are two major approaches to the determination of the purity of a chemical compound. The first is the absolute approach, based on thermodynamic methods; the total amount of impurities can be determined without detailed knowledge of these impurities. The second is the chromatographic approach, which gives information about the detection and determination of impurities as far as their nature and chemical behaviour are known. Impurities may be derived from different origins. Synthesis precursors, intermediates and side-reaction products are intrinsic impurities. In addition decomposition products, unwanted isomers and polymorphs may appear as impurities. The evaluation of impurity levels is the basis for specifications of drug substances. A total proportion of impurities of less than 1% seems to be a reasonable goal. Identification of impurities present in proportions estimated to be 0.1 % and above is also required. Finally, the setting of specification limits depends on a combination of factors based on knowledge of the chemistry and pharmacology of the components and the economics of the process.
Van Rompay
J
J
Janssen Pharmaceutica, B-2340-Beerse, Belgium.