LC/MS/MS QC drifting during run of 96 samples

[mabrams0828]

I am running a Sciex 3200 LC-MS/MS system for Pain Management toxicology. Our panel consists of 32 analytes. We run 96 patients along with a set of QC (low/mid/high) at the start of the run then another set in the middle and a third set at the end of the run. We are finding that the second and third set some analyses can be >2SD and >3SD out of range where the first set is fine. We have investigated our sample preparation and have ruled that out. We have reinjected that run on another instrument and the QC pass.It happens on more than one instrument. We recently had a couple our instruments deep cleaned Q1 and Q3 cleaned but we still see this issue. We find the analyses it happens the most include: oxymorphone and alprazolam and alpha hydroxyalprazolam. Has anyone else experienced this or does anyone have any suggestions to help us troubleshoot this.

[James_Ball]

I am running a Sciex 3200 LC-MS/MS system for Pain Management toxicology. Our panel consists of 32 analytes. We run 96 patients along with a set of QC (low/mid/high) at the start of the run then another set in the middle and a third set at the end of the run. We are finding that the second and third set some analyses can be >2SD and >3SD out of range where the first set is fine. We have investigated our sample preparation and have ruled that out. We have reinjected that run on another instrument and the QC pass.It happens on more than one instrument. We recently had a couple our instruments deep cleaned Q1 and Q3 cleaned but we still see this issue. We find the analyses it happens the most include: oxymorphone and alprazolam and alpha hydroxyalprazolam. Has anyone else experienced this or does anyone have any suggestions to help us troubleshoot this.

If you requeue the entire sequence and let it run a second time right after the first, does it follow the same trend? Just wondering if something is not reaching equilibrium until you get further into the sequence.

Could there be something partially blocking the inner orifice, like a salt from the mobile phase building up over time? Is the curtain gas set to 20 or higher, that helps keep things like that out of the orifice.