Analysis of Residual Catalysts in Pharmaceuticals Using ICP Atomic Emission Spectrometry

Introduction

In addition to containing active ingredients, pharmaceuticals contain a number of components that are intentionally added to improve their properties, as well as residual nonintentional components such as starting materials and intermediates, byproducts, products of decomposition, and reagents and solvents used in the production process. One such component is metallic catalysts, which have been classified as inorganic impurities in the Revised Guidelines on Impurities in New Drug Substances (No. 1216001, issued by the Evaluation and Licensing Division, the Pharmaceutical and Food Safety Bureau (Iyaku Shokuhinkyoku Shinsa Kanrika) on December 16, 2002)1 . Testing methods and other appropriate methods found in the Japanese Pharmacopoeia were directed towards evaluation at the drug development stage. On the other hand, turning to overseas, the European Medicines Agency (EMEA) published guidelines2 on February 21, 2008 that specified the limits for residual metal catalysts or metal reagents that derive from the pharmaceutical production process; it set the permissible limits for 14 types of metals. Further, the United States Pharmacopeia (USP) proposed a new metal testing method and the permissible limits for 31 types of metals in the Pharmacopeial Forum 34(5) (September-October 2008)3 , all of which is indicative of the growing interest in metal impurities in pharmaceuticals. Testing methods that are often used for analysis of metal elements include atomic absorption spectrometry, ICP atomic emission spectrometry, and ICP mass spectrometry, but from the perspectives of speed and simplicity for multi-elemental analysis, using the ICP analytical method is most convenient. Here, the analysis of the 14 types of metals subject to the EMEA guidelines will be used to introduce the inductively coupled plasma atomic emission spectrometry method.

April 21, 2010 GMT