Residual solvents are volatile organic chemicals that are used in the synthesis of complex drug products such as nanomedicines and manufacturing/purification of active pharmaceutical ingredients (APIs) and excipients [1]. The key methodology for analysis of residual solvents is gas chromatography (GC) with various sample introduction techniques such as static/dynamic headspace analysis, solid phase microextraction, or direct injection of the analyte into the GC [2].
Dimethyl sulfoxide (DMSO) is a polar aprotic solvent having low vapor pressure and high solubility for organic compounds and hence commonly used as a solvent in headspace-GC. DMSO is known to coelute with other organic solvents such as N-N’-dimethylformamide (DMF), N-N-Dimethylacetamide and benzyl alcohol in HS-GC. However, the headspace technique is not suitable for less volatile analytes such as DMSO as the analyte may not reach the injector and column due to lack of static equilibrium between liquid and gaseous phases. Consequently, the quantitation of high boiling/semi-volatile solvents becomes challenging. In addition, low volatility impacts the method sensitivity. Therefore, direct injection gas chromatography is the preferred method for quantitation of DMSO [3].
This protocol describes the procedure for quantitation of DMSO using direct injection gas chromatography with flame ionization detection (FID). Herein we used a PerkinElmer Clarus® 690 GC. Methanol was used as the diluent and an Elite 624 (Crossbond 6% cyanopropyl phenyl 94% dimethylpolysiloxane) 0.32 mm ID x 30 m with 1.8 μm layer capillary column was used for the separation.