Drug safety, drug quality, drug analysis.

Controlling and minimizing the side effects of drugs are the key issues in assuring the safety of drug therapy. Since side effects are inherent properties of the drug material, these cannot be influenced by drug analysts. At the same time drug analysts play a predominant role in assuring the quality of bulk drug materials and drug formulations and this is also closely related to the safety issue. The three main attributes of drug quality are identity, strength and purity. Of these, in the case of bulk drug materials, purity is of prominent importance: by the identification (structure elucidation) and quantitative determination of the impurities and degradation products, the risk of their contribution to the side effect profile of the drug materials can be avoided or at least controlled/minimized. The development in the field of chromatographic and spectroscopic methods in the last decades has led to changes in the philosophy, structure and requirements in the monographs of drug materials in the principal pharmacopoeias. Although the approaches of the European and US Pharmacopoeias are somewhat different, a common feature is the shift of focal point toward purity tests. In contrast to this, relatively few changes are observable in the field of the assay methods for bulk drug materials: non-selective titrimetric and spectrophotometric methods are still widely used. Since the results of these do not contribute to the safety issue, the omission of these tests and substitution by the "mass balance" concept is recommended. The effectiveness of the tendency of replacing non-selective methods by selective ones (mainly HPLC) is also questionable. The reason for this is that due to the limited precision of the HPLC assay the drug content obtained by the mass balance concept is a much better quality control attribute for bulk drug materials than that obtained by HPLC. It is recommended that classical assay methods (including HPLC) be used in exceptional cases only and the time and energy thus spared be used for more important impurity-related issues that directly contribute to the safety of drug therapy.