Determination of Elemental Impurities in Pharmaceuticals by HR-ICP-OES according to ICH Q3D and USP 232 and 233 Application Note · PlasmaQuant 9100 Elite

Introduction

As of January 2018, pharmaceutical products must comply with specified limits for the allowed exposure to certain trace elemental impurities. The maximum permitted exposure limits and the analytical methods in order to quantify the listed trace elemental impurities are described in the United States Pharmacopeia (USP) chapters <232> Elemental Impurities – Limits and <233> Elemental Impurities - Procedures and are aligned with the International Conference on Harmonization (ICH) Q3D Step 4 guidelines.

As discussed below, ICP technology is now a compendial method for the quantification of trace elemental impurities and is becoming the routine method of choice for manufacturers and suppliers of pharmaceutical products, including raw materials, drug substances and excipients. Challenges within this field of application include a large variety of sample types with diverse analyte combinations and target limits. This, in turn, requires ICP instrumentation that can handle a large variety of sample types with varying matrix loading and solvent types (e.g., aqueous or solvent based) and offers the measurement of a wide concentration range. In this regard, the plasma system needs to be able to handle any sample type without compromises in plasma stability and robustness. The accurate and reliable quantification of trace elemental impurities also requires a high sensitivity of the system, as well as the ability to resolve spectral interferences that are common in ICP-OES.

Within this study, the PlasmaQuant 9100 Elite high-resolution ICP-OES is used in order to determine elemental impurities in pharmaceutical products containing folic acid as the active pharmaceutical ingredient (API). Folic acid is used as the API in tablets as well as in liquid pharmaceutical products, which are administered orally or via injection (parenteral).

As will be shown below, the exceptionally high spectral resolution and sensitivity of the PlasmaQuant 9100 Elite offers new analytical potential. It allows for an interference-free analysis of trace elements in any matrix and any elemental constellation. Furthermore, the high plasma robustness of the High-Frequency Generator and the sample introduction system with its centerpiece, the V-Shuttle torch, allow for the analysis of pharmaceutical products with excellent accuracy and precision. The DualView Plus feature additionally offers the measurement of a wide concentration range within a single measurement. This often avoids the need for measuring several dilution samples in order to collect data for elements in both