I have a high pressure mixer, binary pump HPLC system with an autosampler (Beckman 125 pump, 508 autosampler, 166 detector). After a long period of troubleshooting injection-to-injection reproducibility, I was able to determine that enabling the air segment option in the autosampler settings produced more consistent injection volumes (as measured by the total area count after integration, %RSDs that were in excess of 4 or 5 dropped down to 0.2-0.5). This is for a partial loop fill, obviously putting a smaller loop and doing a full loop fill would be a better long term solution, but it's more convenient to be able to vary the injection volume without making a change to the hardware.
My question is: Are there any negative consequences to injecting that air-segment? Is it just going to immediately be dissolved in the mobile phase, due to the high-pressure nature of the system? Do small amounts of air disturb the packing at all, if they aren't fully dissolved?