A Universal Quantitative Residual Solvent Analysis of Solids and Liquids Using a Full Evaporative Technique and Methanized Flame Ionization Detection.

Residual solvent analysis is a common method used in the manufacturing of finished goods and pharmaceuticals to ensure the safety of the final product to the consumer. Typically, this involves a headspace sample introduction set up and then separation by gas chromatography (GC) with detection by a flame ionization detector (FID). This analysis can be very time consuming in sample preparation, calibration and analysis time. A full evaporative technique has been applied to both solid and liquid samples for the rapid vaporization of the solvent analytes, which is then introduced to a GC for separation. Additionally, a methanizer was used in line with the FID creating a uniform response for solvents of various heteroatoms and functionalities. This combination of full evaporative technique with a methanized-FID allows for the use of a single response factor for residual solvent analysis with demonstrated repeatability of ˂4%RSD. Spiked solid sample analysis shows recovery between 95% and 105% of solvents tested at ⁓2 μg of each analyte. Overall, the combination of full evaporative headspace sampling and methanized-FID can be applied to any sample matrix for any solvent used in manufacturing or production, making a universal method for residual solvent analysis.