Heavy Metal Analysis according to ICP/MS
Element determination using ICP/MS in the pharmaceutical sector
The changes in the field of heavy metal analysis in the pharmacopoeias could not be greater: On the one hand, the ICH Guideline Q3D, published in December 2014, has set itself the goal of harmonizing the approval requirements of various regulations. On the other hand, USP <231> previously required a visual limit value test, which is now being replaced by an element selective and quantitative instrumental measurement technique in accordance with USP <232> and USP <233>. The Ph. Eur. also recently published new regulations with chapters 5.20 and 2.4.20.
Due to the large number of analytes and the low determination limits to be achieved, element determination using ICP/MS has become immensely important in the pharmaceutical sector. Eurofins BioPharma Product Testing (former Eurofins Fintelmann and Meyer GMP) have been a reliable partner in this field for many years.
ICH Guideline Q3D
The final version of the ICH Guideline Q3D ("Elemental Impurities") was published in December 2014. Based on the evaluation of toxicological data, limit values for 24 elements were established for various routes. As part of a risk assessment of the production process, the manufacturer is to identify known and potential sources of impurities and control them on the basis of these limit values.
The aim of this guideline is to harmonise the different approval requirements of regional regulations. However, the provisions of USP and EP show considerable differences in implementation both with regard to the selection of the elements and the determination of the limit values.
USP <232> and <233>
The over 100 years old, unselective and interference-prone visual heavy metal test according to USP <231> ("Heavy Metals") has served its purpose. The new chapters USP <232> ("Elemental Impurities - Limits") and USP <233> ("Elemental Impurities - Procedures") already apply to all new registrations in the American region. This test will be mandatory from January 2018 for approval tests of existing approvals and for all monographs of active ingredients and excipients.
In these chapters, limit values for 15 elements in pharmaceutical products are established and testing using ICP/MS or ICP/OES is defined as the standard method. The scope of the testing will be determined by a risk-based estimation of those elements that can enter the final product naturally, by addition or unintentionally. Therefore, an analysis of all 15 elements is not necessarily required.
EP 5.20 and 2.4.20
In EP 5.20 ("Metal catalysts or metal reagent residues") limit values for 14 elements from metallic catalysts or reagents were defined. Requirements for the determination method are regulated in EP 2.4.20 ("Determination of metal catalysts or metal reagent residues").
The new regulations apply to all substances for pharmaceutical use, whether monographs or not. They will be binding from September 2018, until then a transitional regulation for already existing products will apply.
We support you with our ICP/MS portfolio when it comes to proving the conformity of your products with the new guidelines:
A useful tool in risk assessment of the manufacturing process, providing a quick and cost-effective overview of the presence or absence of many elements. In this way, conspicuous elements can be identified and, if necessary, quantified.
Very effective when it comes to getting an initial overview of the content of certain elements. In the risk assessment process, for example, the elements subject to control can be monitored for exceeding a warning limit.
Element Determination according to…
ICH-Guideline Q3D ("Elemental Impurities")
USP <730> ("Plasma Spectrochemistry")
USP <232> ("Elemental Impurities – Limits"),
USP <233> ("Elemental Impurities – Procedures")
EP 2.2.58 ("Inductively coupled plasma-mass spectrometry")
EP 5.20 ("Metal catalysts or metal reagent residues"),
EP 2.4.20 ("Determination of metal catalysts or metal reagent residues")
This method allows an accurate determination of the content of elements in accordance with the above regulations.
Both pharmacopoeias require that a matrix validation be performed to demonstrate that the analytical method is specifically applicable to the respective matrix. In the respective monographs there are exact specifications for the parameters to be observed. We would be pleased to advise you on this subject and send you an offer.
As a service provider in the field of drug testing, we can look back on over 90 years of experience and have been GMP certified for more than 20 years.
We offer you all services from a single source - regardless of whether it is a matter of chemical or microbiological testing of active ingredients and auxiliary substances, herbal drugs, cosmetics or additives.
Should we not be able to carry out an analysis ourselves, we have 225 laboratories worldwide with over 150,000 methods at our disposal to solve your problem. Of course we take over the coordination for you. On request, our experts will also be happy to advise you directly at any time.
Each incoming package is registered immediately, even before it is unpacked. The sample is first checked for integrity and storage conditions and registered in our laboratory system. From this point on, each sample vessel is unmistakably marked with a barcode. Each step is, of course, carried out in accordance with the 4-eye principle. In addition, you have the option of tracking the sample status on the Internet at any time. This goes from the sample registration, over the release of the results up to the certificate, which we make available to you of course also on-line.
Upon request, we will gladly send you our template for a delimitation of responsibility contract.
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