Problem: The United States Pharmacopeia (USP) is proposing two new General Chapters on levels of trace element impurities in pharmaceutical products with the aim of:
- Updating the methodology used to test for elemental impurities in drugs and dietary supplements to include procedures that rely on modern analytical technology; and
- Setting limits for acceptable levels of metal impurities (including, but not limited to, lead, mercury, arsenic and cadmium) in drugs and dietary supplements.
The proposed USP chapters 232 and 233 will place greater emphasis on the use of automated detection methods for analyses.
The current USP chapter is based on precipitation-based detection methods for analyses, however these methods do not deliver the high level of accuracy necessary and can lead to false negative results. As a consequence, trace elements are not being fully detected in pharmaceutical products.
Solution: The USP is proposing a change to legislation that will lower limits for trace elements in pharmaceuticals. New methods of analysis will use instrumentation–based methods rather than the traditional wet chemistry-based techniques, with inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectrometry (ICP-OES) as the technologies of choice.
ICP-OES works on the principle of introducing a liquid sample into the plasma via a nebulizer. The nebulizer then turns the liquid sample into an aerosol. Within this plasma the sample is heated up and as a result emits light which is then measured. Light given off by a specific metal has a discrete wavelength and the intensity of that light is proportional to the concentration of the element within the solution. With the use of this technique, scientists are able to accurately and easily determine levels of trace elements in pharmaceutical products. High throughput is an additional advantage of ICP-OES, which typically takes two minutes per sample analyzed. This is in contrast to wet chemistry-based methods, currently used by the USP, which often require up to 24 hours for sample preparation alone.
The Thermo Scientific iCAP 6000 Series ICP-OES and Thermo Scientific iTEVA Software are ideal for the analysis of trace elements in pharmaceutical products. The instruments are extremely powerful with low detection capabilities and have the ability to resolve complex spectra. In addition, the iCAP 6000 Series ICP-OES has the required wavelength range for the analysis of 167 nm to 847 nm and enables the analysis of all the elements that emit light between these two values. This is significant for a number of reasons. The low wavelength access enables the most sensitive wavelengths for As and Hg to be reached while the instrument also has the ability to access interferencefree wavelengths which are critical when analyzing elements that produce a high number of emission lines such as Os, Ir, Pt and Pd. A solid state swing frequency 27.12 MHz RF generator offers robust plasma generation to deal with the most challenging sample matrices. An example of how this is particularly useful is when analyzing parental solutions which contain high concentrations of sugars and salts which can lead to a loss of power within the plasma, resulting in decreased sensitivity.
With the introduction of the new USP chapters on the horizon, the implementation of ICP techniques offers numerous advantages to pharmaceutical laboratories for the detection of trace elements. By using the automated method of analysis provided by the iCAP 6000 Series ICP-OES, laboratories are offered a wealth of benefits including ease-of-use, minimal training, high throughput and the capability to efficiently identify trace elements at lower limits, ensuring compliance with the requirements of this new legislation.
For more information, visit www.thermoscientific.com/trace