A quality concept for impurities during drug development - use of the hyphenated LC-MS technique

A quality concept for impurities during the drug development process is proposed based on the requirements featured in the impurity guidelines of the International Conference on Harmonisation. Because of the particular nature of the drug development process, one crucial element is qualification. Once an impurity profile is qualified by the first toxicological studies, attention is then focused on the comparison made, by means of comprehensive analytical monitoring, between qualified impurities and those of new batches. The clear assignment of impurities to toxicologically-qualified impurities can be addressed using multidimensional information, such as retention times, molecular mass or spectral properties. The advantages of use of the hyphenated LC-MS technique in performing this 'impurity inventory' are discussed by the authors using the example of peptide drugs.