The water content of active pharmaceutical ingredients (APIs) is a key parameter in quality control, helping to ensure shelf life and proper function when used in medical treatment. KF titration is the method of choice for these water content determinations because it is selective for water.
To ensure accurate determination of water content, it is important that samples possess good solubility in KF solvents and release water completely. There are various methods to address poor solubility, including the introduction of solubilizers to the titration cell. However, this approach has limitations, including the potential for side reactions with the sample, and the risk of decreased cell conductivity if solubilizers are added beyond a certain percentage. This challenge can be overcome by introducing heat to the sample solution.
In this article, we will discuss a Karl Fischer (KF) titration method that can improve the solubility of sample solutions, leading to more precise and efficient analysis. Specifically, we will examine a direct addition technique that utilizes a thermostatable vessel. By adopting this technique, we can achieve better solubility, resulting in more complete water release and more accurate determination of water content in antibiotics.
Experimental
In order to increase the solubility of the Amoxicillin aliquot, the EVA V3 titrator and a special thermo vessel (thermostatable vessel, as shown in Figure 1) were used to perform the measurement. The temperature was set to 50 °C. After an initial heating period (~20 minutes), ~50 mg powdered sample was added directly into the titration cell with a weighing boat and the KF titration started. A mixing time of 120 seconds ensured dissolution, and the correct sample weight was obtained by back-weighing. This was repeated six times.
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Figure 1. EVA V3 Karl Fischer Titrator and a thermostatable vessel. |
Results and discussion
In order to dissolve the sample solution, a thermostatable vessel was utilized. However, applying heat has the potential to cause over-titration. To prevent this potential issue, the EVA titrator with the cautious titrant addition was used. By implementing these parameters, accurate titration results can be achieved.
The results of water content analysis for all six antibiotic aliquots using direct injection volumetric titration are presented in Table 1. It indicates a mean water content of 9.55 ± 0.25%.
According to the results displayed in Figure 2, the KF titration reactions of the six samples reached their endpoint within a range of 60–65 seconds. These results suggest that this technique enables fast and efficient analysis.
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Table 1. Results of water content for six Amoxycillin aliquots. |
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Figure 2. Titration curves of six Amoxycillin aliquots (current in µA vs Time in seconds). |
Conclusion
The METTLER TOLEDO EVA V3 volumetric Karl Fischer titrator is a highly effective solution for determining water content in challenging samples such as those that are insoluble. With its thermostable KF vessel and advanced features, this system delivers fast and reliable results with outstanding precision and accuracy.
