The various techniques of Raman spectroscopy find a wide range of applications in the different areas of the pharmaceutical industry, be it for the detection of counterfeits, as an in-process control (IPC) during the production of the active pharmaceutical ingredient, for content determinations, as an ID test for vaccines, for the simultaneous determination of several product quality attributes (PQAs) as part of a rapid release strategy, up to sterility tests, to name just a few examples [1-4].

Risk assessments are a good thing and can make life easier in the pharmaceutical environment. Everywhere it is said that this or that has to be or has been defined "risk-based"...

Hmm, all well and good, but where are the potential applications in the validation of analytical methods?

We’d like to make a deep dive into this question in today's blog post.

In lyophilizates of pharmaceutical drugs, the residual moisture content must be determined. It must be as low as possible in order to delay possible degradation reactions during storage and thus ensure the declared shelf life. Such a water determination can be performed applying the Karl Fischer titration. This titration method is a widely used procedure for quantitative water determination in a variety of samples and was developed by Karl Fischer in 1935. In the European Pharmacopoeia (Ph. Eur.), chapter 2.5.12 covers the volumetric (semi-micro) determination and chapter 2.5.32 covers the coulometric titration. The choice of method is primarily based on the amount of water present in the sample.

Purity determinations are applied as part of the quality control of pharmaceuticals, their active pharmaceutical ingredients (and, if applicable, their excipients in case they are not yet obtained in compendial quality). This includes quantitative determinations, resulting in a definite statement of the quantity or concentration, as well as qualitative / semi-quantitative determinations with results allowing only conclusions to be drawn as to whether the impurity is present or not or whether it is below a certain limit value. Such determinations are also known as "limit tests". Some people will think back to a laboratory practical training in drug analysis during their studies with more or less enthusiasm when they hear the word "limit test"...