Thermal desorption-Gas chromatographic methodology for the determination of residual solvents in mesoporous silica

- Novel approach for the determination of residual solvents in drug loaded mesoporous silica.
- A variant of thermal desorption-gas chromatography was optimized and validated.
- New methodology gives similar results than more complex conventional procedure.

In this work, thermal desorption-gas chromatography-flame ionization detection (TD-GC-FID) was adapted to enable the determination of residual solvents (RS) in mesoporous silica (MPSi). MPSi is often utilized in various pharmaceutical formulations or drug delivery systems and the accurate determination of RS is an important part of pharmaceutical quality control. Seven commonly used solvents (methanol, ethanol, acetone, isopropanol, dichloromethane, tetrahydrofuran and hexafluoroisopropanol) were evaluated in combination with 3 types of MPSi having pore sizes of 2-3, 15 and 25 nm. Validation results showed general recovery values > 98% and good linearity over the concentration ranges studied. The limits of detection (LOD) and limits of quantification (LOQ) for the different solvents ranged from 0.03 to 0.08 μg and from 0.1 to 0.2 μg per tube, respectively. Verification of the accuracy of the TD method was investigated by using an alternative method based on complete dissolution of MPSi in hydrofluoric acid (HF) followed by full evaporation headspace-GC (HS-GC). The results obtained from both procedures were not statistically different (p > 0.05) when applied to actual experimental drug samples consisting of itraconazole loaded on MPSi.