Hi Babak,
We've encountered this issue before - ISTD suppression at high analyte concentrations due to ionization competition.
Perhaps try:
(1) Alternative ionization techniques (e.g., switching between ESI+/- or APCI)
(2) Mobile phase modifiers - consider using ammonium salts
(3) Dilution, followed by injection on a more sensitive MS
Good luck!
Stephanie
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Stephanie Cape Ph.D.
Senior Director, Precision Medicine Delivery
Labcorp
[email protected]Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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Original Message:
Sent: 10-21-2025 15:28
From: Babak Basiri
Subject: Decrease in MS response of SIL internal standard with increasing analyte concentration
Hi all,
We are using a SIL internal standard for LC-MS assay development to quantify a small molecule analyte. In our calibration curves, there's a systematic DECREASE in the MS signal of SIL IS as the analyte concentration increases in calibrators. It appears as if the analyte is interfering with the ionization of the SIL IS.
Have you ever seen a phenomenon like this? Any recommendations on how to solve it?
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Babak Basiri
Director, ADME/PK
Dyne Therapeutics
Waltham MA
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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