Isotopic Distribution Calibration for Mass Spectrometry.

Area of Science:

• Analytical Chemistry
• Mass Spectrometry

Background:

• Mass spectrometry (MS) is crucial for sensitive and specific analyte detection and quantification.
• Current MS quantification relies on complex, resource-intensive external calibration curves and internal standards (IS).
• Existing methods are particularly challenging for multi-analyte measurements due to variability across instruments, samples, and runs.

Purpose of the Study:

• To develop a simplified and more efficient internal calibration method for mass spectrometry.
• To enable accurate quantification of multiple analytes simultaneously.
• To provide mathematical correction for suboptimal experimental conditions in MS.

Main Methods:

• Developed an internal calibration method using the natural isotope distribution of an analyte's internal standard (IS).
• Utilized multiple isotope distribution calibrators for multiplex quantification within the same sample.
• Applied the method to high resolution, accurate mass MS for various analytes, including lower molecular weight compounds.

Main Results:

• The internal calibration method effectively uses natural isotope distributions for multipoint calibration.
• Demonstrated successful multiplex quantification of different targets in a single sample.
• Showed that the approach allows mathematical correction for suboptimal experimental conditions and can potentially quantify difficult targets.

Conclusions:

• The developed isotope distribution calibration method offers a simplified, resource-efficient alternative to traditional MS quantification.
• This approach facilitates accurate multiplex quantification and improves robustness against experimental variability.
• The method holds promise for enhancing the capabilities of automated MS platforms and quantifying challenging analytes.