To find out the best choice for your task you can go through a few questions and answer them for yourself. Following are the questions that you need to answer before selecting reference standards for your analytical tasks and pharmaceutical quality control in testing laboratories.

Questions you need to answer before selecting analytical reference standards

1.      If you are working according to the monograph method or if you are using your in-house method?

If the answer is yes, I am using the monograph method, the best choice would be the analytical reference standards from the corresponding pharmacopeia because it is designed for that special use. Alternatively, you can use a secondary reference standard that has been established by comparison to the pharmacopeia reference standard.

If the answer is no, I’m using an in-house method, then it could be better to consider referenced and that's other than those of the pharmacopeia. Because the pharmacopeia reference standards do not necessarily seem to be built for that application. The pharmacopeia is guaranteed the suitability of their reference and that's only if they are used in combination with the monograph method otherwise it is up to the user to ensure the suitability of the reference standard. And it is observed that pharmacopeia reference standards have been challenged seriously for an Alf monograph news so let's have a look at the alternatives.

2.      If you are looking at an API or an impurity?

If you are testing an API, the properly characterized primary reference standard would be the best choice. Definitions of primary reference standards and guidance on how to obtain them are available from several sources like WHO, FDA, ICH Q7 guideline, or EP general chapter 5.12. The characterization that is needed to obtain a reference standard that is suitable for your purpose depends on how you answer the next question.

3.       Do you want to identify the API or do you want to quantify it?

The identification of a qualitative reference standard with a silver purity estimation by HPLC is sufficient. While the quantitative primary reference standard requires an accurately assigned assay. We will have a closer look at that on the next question. 

On the other side, if you are looking at an impurity you can use an impurity reference standard which is usually characterized less extensively than a primary API reference. Nevertheless, again the necessary characterization steps depend on whether you want to identify or quantify the impurity.

Characterization of the different analytical reference standards

For a qualitative reference standard, the identity of the material must be ensured. So, for both primary API reference standards and also for the impurity reference standard, that is recommended to verify the identity by several orthogonal methods. Not all of the listed methods need to be applied but recommended is doing at least three, for instance, NMR spectroscopy, mass spectrometry, and IR spectroscopy. Furthermore, the purity of the material should be checked by HPLC or GC because if the purity is too low the interpretation of the spectra could be difficult.

Regarding the quantification, the recommendations are different for primary reference standards and impurity reference standards. For impurity referenced standards the assay is usually assessed by a 100% method. To calculate the assay properly, purity water content and residual solvent content need to be determined. The same is done for the primary reference standards but in that case, it is recommended to additionally determine the assay by a second independent method, for example, QNMR or titration. Furthermore, organic residues should be determined.

Learn about prescribed guidelines by ICH Q7 on handling of primary and secondary reference standards

Symtera Analytics is a certified supplier of analytical reference standards, having a wide range of primary and secondary reference materials for both API and impurity. This exclusive variety of reference material can be used in several industries including pharmaceutical, beverage, dairy, pulp & paper, wine, and many more. If you are looking for analytical reference standards, contact us to share your requirements for authentic and custom solutions.