Rapid Equilibration of Samples for Residual Solvents Analysis by Static Headspace – GC-VUV

Figure 1. Overlaid residual solvent chromatograms for 40, 20, 10, 5, and 2.5 min static headspace equilibration times at 80°C. The Gerstel MPS2 with shaking and heating established quick equilibration between sample diluent and headspace even when using a retentive solvent like DMSO. 200mg of sore throat spray in 2mL DMSO:water (1:1) was spiked with the residual solvents at 0.5x the ICH concentration limits.

Figure 2. Water-miscible acetonitrile (MeCN) comes to quick equilibration with the Gerstel MPS2 static headspace autosample, as seen in the overlaid chromatograms for 40, 20, 10, 5, and 2.5 min equilibration times at 80°C. The sample was 200 mg of sore throat spray in 2 mL DMSO:water (1:1) with the residual solvents at 0.5x the ICH concentration limits.

Figure 3. Unlike in the previous work with water as the diluent where Tetralin was still equilibrating at 40 min, equilibration is quickly established for DMSO:H2O (1:1). Tetralin is the least volatile of the Class 2 solvents typically sampled using static headspace.

Figure 4. For most Class 2 residual solvents, headspace partitioning is better when using water as the pharmaceutical product diluent. When water-insoluble articles are dissolved in DMSO, an effective way of increasing residual solvent detectability through better headspace partitioning is to dilute the DMSO sample with water 1:1. The sample was 200 mg of sore throat spray.