Journal
ANALYTICAL CHEMISTRY
Volume 92, Issue 11, Pages 7690-7698Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.0c00633
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Funding
- National Key Research and Development Program of China [2018ZX09734-003]
- National Key Research and Development Program [2017YFC0909303]
- Guangdong Provincial Science and Technology Project [2017B020234005]
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The present project studied the signal drift in liquid chromatography tandem mass spectrometry (LC-MS/MS) and proposed a strategy for compensating such drift. In the study, four 4-component groups were repeatedly run on different LC-MS/MS systems for over 12 h to investigate the dependence of signal drift on time and hardware systems. The 4-component groups each consisted of (1) an analyte, (2) a stable isotope labeled analyte, (3) a compound with similar structure to the analyte, and (4) a compound with dissimilar structure. All of the species showed significant signal drift, generally more than 25% over 12 h. The analyte and its stable isotope labeled analog always have the same drifting pattern including the trends and direction from one LC-MS/MS system to another. Signal drift was also found to be concentration dependent. Our experiments further proved that a conventional stable isotope labeled internal standard in LC-MS/ MS quantification would not compensate the variations caused by concentration-dependent signal drift. An ideal internal standard for LC-MS/MS has both identical structure and similar concentration to the analyte. For that, we proposed a new internal standard strategy, pseudo internal standard (Pseudo IS), for LC-MS/MS quantification. Pseudo IS could effectively compensate signal drift in spite of its significant time, system, and concentration dependencies.
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