The toxicity and potential harm of inorganic contaminants that can enter the drug manufacturing process through raw materials, catalysts, machinery, and packaging, are recognized and require monitoring and control.  Limits for elemental impurities have reached broad consensus thanks to the efforts of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and USP, and these regulatory bodies continue to update guidance and modernize methodologies.  Shimadzu offers a wide range of solutions for ICP-OES, ICP-MS, and X-ray fluorescence that meet the needs of USP <232> and <233> today and prepare your lab for future regulatory demands.  Anticipated changes mean that ICP based techniques will continue to grow in prevalence, and we provide not only the instrument, but ensure data integrity for your compliant environment using the LabSolutions informatics platform.  With the sensitivity of ICP-MS for multi-element analysis, the ability to couple ion chromatography for heavy metal speciation, and the potential to eliminate sample prep with the EDX, we have the flexibility to fit your workflow.

Featured Webinars

Webinar - Validation of Quantitative Method for Determination of Elemental Impurities in Pharmaceutical Products Following USP <232>/<233> on ICPMS-2030


24 targeted elemental impurities in three drug products were determined following new USP chapters <232>/<233> using Shimadzu ICPMS-2030. The method was evaluated and validated according to the procedures defined by USP <233> and combined with microwave digestion for sample preparation. Good calibration linearity, repeatability, stability and specificity were achieved for all 24 impurities. Low LODs and LOQs were obtained as compared to the target limits from USP <232>. The ICP-MS method applying universal He collision mode provides a high throughput method for routine elemental impurity analysis in pharmaceutical products.

Webinar - EDX: A Fast & Simple Technique for Pharmaceutical Elemental Analysis


AA or ICP-OES/MS is often viewed as the gold standard to analyze elements during the pharmaceutical manufacturing process, from drug discovery to the QA/QC of final formulations. While extremely accurate, these techniques have the downside of requiring the sample to be in liquid form when analyzing, resulting in arduous sample-preparation and long analysis time.  In this seminar, we introduce Energy-Dispersive X-Ray Fluoroscopy (EDX) as an alternative technique to perform elemental analysis that requires little sample preparation, is easy to use and can provide results quickly in a variety of pharmaceutical roles. 

Featured Applications

Validation of Analysis Method Using ICPMS-2030 Based on USP <233> ELEMENTAL IMPURITIES - PROCEDURES


In the United States Pharmacopeia General Chapters USP <233>, inductively coupled plasma-mass spectrometry (ICP-MS) is recommended as the analysis procedures. In this paper, validation of the analytical method using a Shimadzu ICPMS-2030 was carried out in accordance with USP <233>. The tested materials were constituent ingredients used in oral formulations. The accuracy, precision, limit of quantitation and specificity of 24 target elements are presented, assuming measurements below the Control Threshold, 30% of the PDEs.

Analysis by ICP Atomic Emission Spectrometry in Accordance with the ICHQ3D Guideline for Elemental Impurities Using ICPE-9820


Here, we conducted analysis of 24 elements according to the ICH Q3D guidelines using the Shimadzu ICPE9820 multi-type ICP atomic emission spectrometer. The ICPE-9820 offers simultaneous all element analysis with high sensitivity and high precision, while delivering high throughput. Low running costs are achieved by a unique combination of the reduced-flow mini-torch and vacuum optics, thereby reducing the overall consumption of argon.

ICH Q3D Elemental Impurities Analysis of Tablets by EDX - Verification Based on USP <233> ELEMENTAL IMPURITIES-PROCEDURES


In the United States, the United States Pharmacopoeia General Test Chapters USP <232> and <233> have been applied to new drug products since January 1, 2018. ICP-MS and ICP-AES are recommended as the analysis procedures in the chapters. However, if the validation requirements are met, the alternative procedure can be substituted for the recommended analysis procedures(1) (2) (3). Therefore, the appropriateness of Energy Dispersive X-ray Fluorescence Spectrometer was verified referring to “Limit Procedures” in USP <233>. The instrument used was EDX-7000 and the test was conducted by evaluating of elemental impurities in oral drugs (tablets). As the target concentration (allowable concentration), the value obtained by dividing 30% of the PDE value by the maximum daily dose was set.

X-Ray Fluorescence Analysis of Residual Catalysts


Many familiar industrial products are made of organic compounds and their manufacturing processes involve various synthesis reactions and metal catalysts. Catalysts are mainly divided into two categories: homogeneous catalysts and heterogeneous catalysts. In general, homogeneous catalysts are used for manufacturing pharmaceuticals and chemicals. While the reactions of homogeneous catalysts can be controlled rigorously, separation of reaction products is difficult. Meanwhile, there is a need to control the amount of residual catalysts in terms of the safety of the products and the re-use of expensive catalysts. For example, the Guideline for Elemental Impurities (ICH Q3D) enforced in April 2017 requires a risk assessment for substances, such as catalysts, that are purposely added during the manufacturing process. This article introduces an example analysis of the amount of residual homogeneous catalyst following a synthesis reaction using the Pharmaceuticals Impurities Screening Method Package; in this example we used palladium (Pd), a substance widely used as a catalyst, for a cross-coupling reaction which is widely used for the synthesis of organic compounds.

X-Ray Fluorescence Analysis of Tablets


Some tablets of drug products have a coating applied to the surface for various purposes, such as preventing deterioration, masking unpleasant taste or smell, or controlling the timing of drug release. Fig. 1 shows an example of a tablet coating. Although inductively coupled plasma-atomic emission spectrometry (ICP-AES) and ICPmass spectrometry (ICP-MS) are generally used as methods for analysis of the elements in drug products, if an entire tablet is pulverized or dissolved, it becomes difficult to differentiate the elements that originate from the coating and other elements. X-ray fluorescence analysis makes it possible to analyze tablets as-is without pulverization. This article introduces an example of a simple analysis of unevenly-distributed like those in coatings, based on a comparison of analyses of pulverized and unpulverized tablets.

ICH Q3D Elemental Impurities Analysis of Drug Substances by EDX


The ICH Harmonised Guideline, Guideline for Elemental Impurities (ICH Q3D) of drug products, (1) requires control of the residual amounts of 24 elements whose toxicity is a concern. This requirement was applied to new drug products from June 2016 in the United States and Europe and from April 2017 in Japan. Application to existing drugs began in January 2018 in the United States and in December 2017 in Europe.

Although the recommended analytical methods for elemental impurities are inductively coupled plasma-atomic emission spectrometry (ICP-AES) (2) and ICP-mass spectrometry (ICP-MS), use of appropriate alternative methods is also permitted when such methods exist. Therefore, the appropriateness of X-ray fluorescence spectrometry as an alternative to the abovementioned methods was verified referring to the United States Pharmacopeia USP (3).