For the analysis of residual solvents in pharmaceutical formulations, sample carryover is minimized with an inert sample pathway, uniform high-temperature heated zones, and a programmable vent purge as described below.

1.Inert sample pathway
One mechanism for carryover is adsorption or reaction of sample components with the materials in the sample pathway. This is a common problem, particularly with older systems. To minimize carryover, choose a headspace system with a non-reactive, non-adsorptive sample flow path.

2.High-temperature zones
A second mechanism for carryover is condensation of sample along the sample pathway. This typically happens when the pathway is not heated uniformly, or is just not hot enough. Again, it is important to choose a headspace analyzer such as the Agilent system that has been designed and tested for thermal uniformity and high temperature operation. Second, it is important to set temperatures high enough to avoid condensation, and to analyze blanks to confirm suitable settings. For example, carryover tests were performed on the Agilent system with alternate vials of water and pure DMI, a solvent that boils at 225 ºC. When the headspace oven was equilibrated at 220 ºC, and the sample loop and transfer line were kept at 250 ºC, the DMI carryover into the water blanks was very low-under 0.003 percent.

3. Programmed vent purge
A third source of carryover is residual sample in the headspace sampling loop. To avoid this, the sampling loop should be purged after the sample has been transferred to the GC. The G1888 Network Headspace Sampler has a unique programmable vent line purge capability that allows you to set a purge time from 30 seconds up to a maximum of the analysis cycle time. Studies have shown that a 20-minute purge time works well to prevent this source of carryover.