Solvent Detection by Means of TG-MS, Pharmaceutically Active Substance-

Sample

Pharmaceutically active substance, recrystallized in an organic solvent

Application

Active ingredient

Conditions

Measuring cells: TGA850, Mass spectrometer (Balzers ThermoStar)

Pan: Alumina 70 µl

Sample preparation: As received, no preparation

TGA measurement: Heating from 30 °C to 350 °C at 10 K/min, blank curve corrected

Atmosphere: Nitrogen, 20 cm³/min

Interpretation

The TGA curves show a number of weight loss steps. Below about 200 °C, a continuous weight loss can be observed. At 210 °C and 270 °C clearly defined steps are visible. The latter steps can be interpreted as the beginning of the decomposition of the product. The weight loss steps at lower temperatures could be caused by the loss of moisture or solvent that is set free on heating. Definite information is only obtained from a measurement in combination with a mass spectrometer.

The intensities of different fragment ions were recorded during the TGA measurement using the MS in the MID mode (Multiple Ion Detection). Changes at m/e = 31 and 43 were observed. These can be assigned to methanol and a fragment of aceton. Both solvents were used to recrystallize the product. From this MS information it is possible to establish the connection between the TGA steps and the solvent detected. While methanol is liberated over a wide temperature range, aceton is set free suddenly. This indicates that aceton was bound more firmly in the substance in the form of a solvate.

Evaluation

Conclusion

In favorable cases the combination of TGA and MS allows the characterization of solvates and makes possible the distinction between absorbed residual solvent and solvent molecules that are more firmly bound in some way.

_{Solvent Detection by means of TG-MS, Pharmaceutically Active Substance | Thermal Analysis Application No. HB843 | Application published in METTLER TOLEDO TA Application Handbook Pharmaceuticals}