An overview of sample preparation procedures for determination of elemental impurities in medicines

Abstract

Elemental impurities determination in pharmaceuticals has become an emerging topic in the last years due to the revision of the Chapter 231 from the United States Pharmacopeia by three guidelines recently implemented: Chapters 232, 233 and 2232. Chapter 233 describes sample preparation and two analytical procedures, i.e. using inductively coupled plasma optical emission spectrometry (ICP-OES) or using inductively coupled plasma mass spectrometry (ICP-MS) for determination of elemental impurities. The main advantages and limitations of these instrumental methods have been well described, however, inherent in performing any analysis is the sample preparation step, which can be considered the most critical part of the analytical procedure. Generally, pharmaceutical samples present a wide range of different compositions, such as excipients, flavoring agents, stabilizers, and active ingredients. Consequently, these complex matrices make sample preparation a challenging step. In this sense, this review intends to discuss the trends, advantages and challenges of proposed approaches for preparation of pharmaceutical samples (active pharmaceutical ingredients, raw materials, pharmaceutical dosage forms, and dietary supplements) for determination of elemental impurities based on published works since 2000. Challenges and suitable alternatives observed during the determination of elemental impurities in pharmaceuticals using ICP-based methods are also discussed.