Identification and Determination of Impurities in Drugs book cover

Identification and Determination of Impurities in Drugs

Impurity profiling is the common name of a group of analytical activities, the aim of which is the detection, identification/structure elucidation and quantitative determination of organic and inorganic impurities, as well as residual solvents in bulk drugs and pharmaceutical formulations. Since this is the best way to characterise the quality and stability of bulk drugs and pharmaceutical formulations, this is the core activity in modern drug analysis.
Due to the very rapid development of the analytical methodologies available for this purpose and the similarly rapid increase of the demands as regards the purity of drugs it is an important task to give a summary of the problems and the various possibilities offered by modern analytical chemistry for their solution. That is the aim of this book.
The book is methodology-oriented. In the first chapter some important aspects of the background of impurity-related analytical studies (toxicological, pharmacopoeial aspects, the characterisation of the sources of impurities and the role of impurity profiling in various fields of drug research, production and therapeutic use) are summarised. Chapter two deals with related organic impurities, the strategies for impurity profiling, the use of chromatographic and related separation methods, spectroscopic, and hyphenated techniques. The subject of the third chapter is the identification and determination of residual solvents. The determination of inorganic impurities is discussed in chapter four. The special problems of degradation products as impurities are dealt with in chapter five. A separate chapter has been compiled to deal with one of the most up-to-date problems in contemporary pharmaceutical analysis, the estimation of enantiomeric purity of chiral drugs. Chapter seven is devoted to various approaches to solve the problem of polymorphic modifications as impurities. Since in the broader sense of the word the microbiological purity of drugs and drug products also belongs to this circle, the most important information from this field is summarised in chapter eight. After the mainly methodology-oriented chapters, the final one concentrates on four groups of drugs (peptides, biotechnological products, antibiotics and steroids) in order to demonstrate the use of the methods described earlier.

For chemists and pharmacists in quality control laboratories of drug manufacturers, drug registration agencies and contract research organisations, and university departments involved in pharmaceutical analysis.


Published: May 2000

Imprint: Elsevier

ISBN: 978-0-444-82899-6


  • Various Aspects of the Estimation of Impurities in Drugs. Introductory remarks (S. Görög). The nature and origin of the impurities in drug substances (S. Görög). Toxicological aspects (R. Lee). The role of impurity profiling in drug research, development and production (S. Görög). Regulatory aspects. ICH and pharmacopeial perspectives (J.P. Boehlert).Identification, Structure Elucidation and Determination of Related Organic Impurities. Strategies in impurity profiling (S. Görög). UV-VIS spectroscopy and fluorimetry (S. Görög). Mass spectrometry in impurity profiling (M. Mák et al.). NMR spectroscopy (Cs. Szántay Jr., Á. Demeter). Planar chromatography (K. Ferenczi-Fodor, Z. Végh). Gas chromatography (GC) and related techniques (A. Laukó). High-performance liquid chromatography (HPLC) and related techniques (M. Gazdag). Determination of drug related impurities by capillary electrophoresis (K.D. Altria). Capillary electrochromatography (CEC) (M.R. Euerby). CEC/MS (S.L. Lane). Supercritical fluid chromatography (SFC) (O. Gyllenhaall). Purity check by differential scanning calorimetry (I. Péter).Identification and Determination of Residual Solvents. Thermoanalytical methods (I. Péter). Gas chromatography and GC/MS (J. Bertram). NMR spectroscopy (G. Balogh). Miscellaneous (S, Görög).Identification, Semiquantitative and Quantitative Determination of Inorganic Impurities. Classical methods (S. Görög). Atomic spectroscopy (A. Lásztity). Other methods (S. Görög).Degradation Products as Impurities (S. Görög). The relation between drug stability studies and the estimation of impurity profiles. Aims, forms and conditions of drug stability testing. Elucidation of degradation pathways. Elucidation of light-induced degradation pathways. Methodological aspects of quantitative drug stability studies based on degradates.Determination of Enantiomeric Impurities. Introduction (S. Görög). Chromatographic methods (S. Görög). Capillary electrophoretic (CE) methods (J. Crommen). Polarimetry, ORD and CD spectroscopy (A. Gergely). NMR spectroscopy (G. Tárkányi).Estimation of Polymorphic Modifications as Impurities in Drugs. The phenomenon and importance of polymorphism (B. Hegedüs). Infrared and Raman spectroscopy (B. Hegedüs). Thermoanalytical methods (I. Péter). X-ray crystallography (M. Bálint).Microbiological Examination of Non-Sterile Drugs and Raw Materials (H. Van Doorne). Introductory remarks. Validation. Total viable count. Tests for specified organisms. Concluding remarks.Selected Examples (Impurity Profiling of Some Groups of Drugs). Peptides (S. Görög). Biotechnological products (K. Ganzler, A.S. Cohen). Antibiotics (A. Van Schepdael et al.). Steroids (S. Görög). Subject Index.


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