Residual Solvent Analysis – No Matrix Effects with the Gerstel MPS2 Static Headspace Autosampler

Jack Cochran, VUV Analytics

Analytical chemists are routinely concerned with matrix effects, which can thwart our ability to accurately quantify compounds of interest.  Lindsey Shear-Laude and I recently tested for matrix effects during our method development for static headspace – fast GC-VUV analysis of residual solvents in pharmaceutical products.

When matrix effects exert themselves at the GC sample analysis stage, it’s usually in the form of response enhancement or suppression.  An example for suppression is a “dirty” sample extract injected splitless that corrupts a GC inlet liner to the point where analytes of interest don’t make it quantitatively to the GC column.  For a static headspace method, it is when analytes are not equilibrated properly because of something in the sample.  One case I’ve seen is excess surfactants in aqueous samples that inhibit partitioning of volatile organic chemicals to headspace, resulting in their reduced response.  We can minimize the potential for these matrix effects with dilution, something that is built into a headspace method for residual solvents since typically only 50-250 mg of pharmaceutical sample is diluted with a few mL of water or another appropriate solvent.

For our simple matrix effects experiment, we employed a Gerstel MPS2 Autosampler with static headspace capability.  This autosampler is very efficient in equilibration of samples for headspace analysis since it allows heat and shaking under user-defined conditions.  Our method used an 80°C incubation temperature, a 90°C syringe temperature, and 10 min shaking, followed by headspace injection to the GC.  The 10-minute sample preparation matched well with our 8-minute fast GC-VUV run for residual solvents (Figure 1). Overlaid chromatograms for four pharmaceutical products spiked with Class 2 solvents ranging in water solubility and volatility demonstrated that sampling was robust, i.e., no matrix effects were seen (Figures 2, 3, and 4).

Figure 1. Static headspace – GC-VUV of Class 2 residual solvents spiked in various pharmaceutical products dissolved in water. The first compound, methanol, elutes at 1.35 min and the last compound, tatralin, elutes in about 6.7 min. Not all solvents are labelled due to space limitations.

Figure 2. Zoomed in chromatogram showing early eluting residual solvents that were spiked into various pharmaceutical products. Except for hexane, the almost perfect overlay indicates a matrix-independent static headspace method. A combination of water miscible and water insoluble solvents is shown.

Figure 3. Zoomed in chromatogram showing mid-eluting residual solvents that were spike into various pharmaceutical products. For this group of compounds, the perfect overlay indicates a matrix-independent static headspace method, even for water-miscible pyridine.

Figure 4. Zoomed in chromatogram showing late eluting residual solvents that were spiked into various pharmaceutical products. Even for relatively involatile solvents the overlay is almost perfect, indicating a matrix-effect-free static headspace method.

Check out my other blog posts on residual solvents analysis using static headspace – GC-VUV.

GC-VUV of Residual Solvents – The Lazy Analytical Chemist

GC-VUV of Residual Solvents – Go with The Flow and Speed Up Your Analyses