Analytical testing is critical for proving that pharma manufacturing processes make the correct product, and that they meet all the required purity standards. These tests have to be developed for every process and product, and must be accurate, reliable, and repeatable. Ideally, the tests will also be user-friendly.
While this sounds straightforward, in reality this is not always the case. In some instances, a potential contaminant might be extremely difficult to detect via standard chromatographic methods, which may necessitate using more complicated and expensive alternative techniques or equipment. In some cases, no viable detection method is available at all. This might be because the molecule is difficult to see, or perhaps the sample matrix is complex, making it difficult to separate out the different analytes.
One method that can be used to make the molecule visible to chromatographic techniques is derivatization. It is often seen as the method of last resort, as there is a perception that it is complicated and labor-intensive. But, in reality, it can be a powerful way to improve the simplicity and accuracy of the testing process for these difficult-to-detect molecules, even when alternative spectroscopic methods exist.
Derivatization offers advantages that go beyond just improving visibility. It can help when an analyte lacks adequate volatility, isn’t sufficiently stable, or cannot be well separated chromatographically from other peaks. Common strategies include silylation, alkylation, and acylation, and the best reactions are quick, reproducible, and produce stable products that can be detected at low levels.
When developing methods at the Siegfried Acceleration Hub, we always look for the fastest, simplest, most accurate option. In certain cases, derivatization proves to be the most effective approach.
In practice, derivatization is particularly valuable when detecting and quantifying trace reagents left over from the API manufacturing process. Examples include ethylenediamine, hydrazine, hydroxylamine, amino carbamates, formaldehyde, and iodomethane. Selecting the right derivatization agent allows these to be transformed into forms that are reliably detected using standard GC or LC techniques.
Although sometimes considered a fallback option, derivatization is often a simple, practical solution to complex analytical problems. By avoiding the need for NMR or specialist detectors — tools not always available in QC environments — it can make routine analysis more accessible and reliable.
At the Siegfried Acceleration Hub based in Grafton, Wisconsin, our team combines deep analytical expertise with state-of-the-art facilities to solve even the most challenging testing problems. From method development to routine QC, we focus on practical, reliable solutions — whether that involves derivatization or other advanced techniques. By keeping early-phase development and analytical work close to home, we ensure faster timelines, stronger regulatory alignment, and seamless collaboration, helping our you move from discovery to commercialization with confidence.