I am developing an LC-MS/MS amino acid method using an Agilent HILIC-Z column. The standard procedure (e.g. AOAC methods) for sample prep, after acid hydrolysis, is to rotovap down and reconstitute, to avoid injecting HCl into the stainless steel LC system. This would create a significant manpower / time burden due to the difficulty of rotovapping aqueous solutions.

I am wondering if it is possible to simply neutralize the HCl with ammonium hydroxide and rely on the MS diverter valve to send the chloride salts to waste. The initial pre-equilibration period at the beginning of each LC run is enough for about 10 column volumes to go to waste (after the injection but before the diverter valve switches). However, I am concerned that with the HILIC phase these ions may still be making their way through the column, and will then end up in the MS. I also worry about the potential impact on retention times, peak shapes, etc. I would verify that salt is soluble at this level, but it also seems like a potential concern. I am still determining exactly what dilution level will best bring my amino acids in range, but I would expect (order of magnitude estimate) between ~2-20 mM ammonium chloride.

Is it a bad idea to treat these samples the ways I'm envisioning? Is there a way to handle a high sample load that doesn't take, like, an hour per sample in the rotovap?