Determination of nitrosamines.
Determination of nitrosamines is one of the pharmaceutical industry’s top priorities. Following the first report of the presence of N-nitroso-dimethylamine (NDMA) in an active pharmaceutical ingredient (API), the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have mandated the identification and control of all APIs and finished products where there is a risk of nitrosamines.
The content of nitrosamines in medicinal products can be controlled primarily by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis. More than that, a reliable analysis result in our offer consists of a well-chosen sample preparation procedure, a selective and sensitive analytical method, and the experience of the analyst, who selects the best method parameters at the optimization stage.
Experience
We have gained experience working with leading pharmaceutical companies. As part of the ongoing work, we have developed analytical methods for small-molecule nitrosamines of 70-150 g/mol. These compounds are mainly formed during manufacturing processes and depend on the presence and type of excipients (e.g. NDBA – N-nitroso-dibutylamine). We have also developed methods for determining molecules with higher nitrosamine drug substance related impurities (NDSRIs). In our work, we focus on achieving the highest possible sensitivity, selectivity and precision. To this end, we individually select the parameters of the methods depending on the composition of the drug and the expected nitrosamines. Due to the above criteria and the required detection limits, we perform nitrosamine impurity determinations using LC-MS/MS workflows based on QTRAP 5500+ and QTRAP 6500+ mass spectrometers (SCIEX).
Our offer
Our offer includes comprehensive development and validation of methods for the determination of nitrosamines in pharmaceutical products. We perform the work according to the client’s criteria and needs based on the EMA note.
At the trial preparation stage, we focus on:
- To achieve the greatest possible recovery of nitrosamines (matrix cleaning);
- reducing additional synthesis of contaminants (selection of appropriate equipment and reagents);
- ensuring the stability of the sample prepared for LC-MS/MS analysis.
During the optimization of the LC-MS/MS method, we solve such problems as:
- Selecting the right internal standard;
- separation of contamination from API;
- Achieving the expected sensitivity of the analytical method.
Quantitative analysis of nitrosamines requires sensitivity, precision and accuracy, which we provide to our customers.
See also: Identification of nitrosamines
