Correction for isotopic interferences between analyte and internal standard in quantitative mass spectrometry by a...

Area of Science:

• Analytical Chemistry
• Mass Spectrometry

Background:

• Stable isotope-labeled internal standards are crucial for accurate quantitation in mass spectrometry (MS).
• A key assumption is the absence of signal cross-talk between the internal standard and the target analyte.
• Naturally occurring isotopes of the analyte can interfere with the internal standard signal, especially for isotopically rich or high-concentration analytes.

Purpose of the Study:

• To address signal interference issues in mass spectrometry quantitation.
• To develop a more accurate data fitting method for situations with analyte-to-internal standard signal contributions.
• To improve the accuracy of mass spectrometry-based assays by accounting for cross-talk and impurity effects.

Main Methods:

• Proposed a nonlinear data fitting approach incorporating experimentally determined constants and an adjustable calibration parameter.
• Applied the method to situations where analyte isotopes contribute to the internal standard signal.
• Also addressed scenarios involving analyte impurities within the internal standard.

Main Results:

• The nonlinear fitting method provides more accurate quantitation when analyte signals interfere with the internal standard.
• The approach effectively corrects for the reverse situation of analyte presence as an impurity in the internal standard.
• Experimental data demonstrated the practical utility and superiority compared to alternative fitting methods.

Conclusions:

• A novel nonlinear fitting approach enhances the accuracy of mass spectrometry quantitation.
• This method is particularly valuable for isotopically rich compounds and complex assay conditions.
• The proposed technique offers a more robust solution for reliable quantitative analysis in mass spectrometry.