Elemental Impurity Analysis - Pharmaceutical Technology

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Elemental Impurity Analysis
The author discusses how to manage pending pharmacopeial changes.


Pharmaceutical Technology
Volume 36, Issue 8, pp. 62-64

Alternative methods

Other techniques can be used in the analysis of elemental impurities, but each must be validated to ensure that it is suitable and able to detect the analytes at the required level. Below are a few options:

Flame atomic absorption spectrometry (FAAS): This simple and relatively cheap technique has relatively high detection limits, especially for elements such as mercury and arsenic. FAAS can only analyze one element at a time.

Vapor generation atomic absorption spectrometry (VG–AAS): This technique involves a chemical reaction to release metals in the form of gaseous hydrides. It has improved detection limits compared with FAAS but can only be used for arsenic, bismuth, germanium, lead, antimony, selenium, tin, and tellurium. Only one element can be analyzed at a time. Reagents are used to generate the hydride therefore generating a higher cost than traditional AAS.

Graphite furnace atomic absorption spectrometry (GFAAS): In this technique, a small amount of sample is slowly heated to first dry then ash the sample. Thereafter, the temperature is raised very rapidly to volatilize the metal of interest. This technique has very good sensitivity and can be used to look at very low levels of analyte similar to those achieved by ICP–AES, but is prone to chemical interferences affecting the results. Also the analysis is slow and can be costly.

The demise of Chapter <231> means that modern techniques referred to above, and others, will now come become more common, and the old wet chemistry results will cease to be valid.

Conclusion

One can only sympathize with the scientists at USP that have responsibility for the standard pharmacopoeial methods involving heavy metals. Of the 4000-plus monographs in the USPNF, there are approximately 1000 that specify a limit of heavy metals, in either a drug substance, excipient, or drug product (4). December 2012 marks the beginning of the end for Chapter <231> and the introduction of Chapters <232> and <233>. By May 2014, <231> will cease to exist, and by this point, validated procedures need to be in place to cover the removal of Chapter <231>. The 18 months between these dates may seem like a long time, but considering the number of existing monographs that contain the limit of heavy metals test, this timeframe seems very short. Overall, the USP changes, although daunting, can lead to improvements for the industry, including by better protecting the public through effectively tested medicines. Manufacturers will have peace of mind that they are providing clean and safe products to the market.

Alan Cross is a scientist at RSSL, Reading Science Centre, Whiteknights Campus, Pepper Lane, Reading, Berks, RG6 6LA, UK, tel. +44 (0)118 918 4129,
.

References

1. O. Pedersoen, Pharmaceutical Chemical Analysis: Methods for Identification and Limit Tests (Taylor & Francis, 2006).

2. N. Lewen et al., J. of Pharm. and Biomedical Anal. 35 (4) 739–752 (2004).

3. ICH, Q3D Impurities: Guideline for Metal Impurities, Final Concept Paper (2009).

4. D.R. Abernethy, Chief Science Officer, USP, presentation online at http://www.usp.org/.


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