Rndirk wrote:
Then the most logical explanation is that, as James said, your analyte is present in the septum of the vial. I find it hard to believe that "a drug" is present in the septum. If it is an interference, it has to be a damn good one to both have the same retention time, and the same MRMs (assuming you're detecting in MRM). If it's indeed MRM, does it have the same ion ratio as your drug?
Another question: is the injection flow through or fixed loop?
As an easy test I suggest to try the same experiment with a vial capped with only aluminum foil.
Or a run with uncapped vial if the solvent is not highly volatile.
I had this same problem when analyzing for Vitamin D. When I extracted my samples in plastic 50ml centrifuge vials I had a hit at the exact same time as Vitamin D with only a very slight difference in the primary and secondary ratio when using MRM. When using glass vials to do the extraction the samples were completely blank. (was doing a study on powdered plumbs to check for Vitamin D). Either Vitamin D is being added to polyproplyene centrifuge vials or there is a phthalate that gives MRM masses that mimics it quite well. I am sure if we had been using tighter mass windows it probably would have not been as bad, but for sensitivity with such analysis most use a unit mass resolution to accommodate any mass drift during the run.
If it is the vial septa, especially if using silicon rubber, you may want to try the caps that have just the thin polypropylene membrane. They won't reseal completely after injection but will still prevent most evaporation for runs lasting a few hours if that vial has to be injected more than once. Natural rubber septa is also an alternative. You just have to see what other septa material is available and find one that works.