Strategies and analytical workflows to extend the dynamic range in quantitative LC-MS/MS analysis

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Chromatography

Background:

• Quantitative analysis using LC-MS/MS can be limited by its dynamic range.
• Extending the dynamic range is crucial for accurate exposure assessment.

Purpose of the Study:

• To evaluate alternative analytical strategies for extending the dynamic range in quantitative LC-MS/MS.
• To assess workflows with and without prior knowledge of analyte concentrations.

Main Methods:

• Two analytical strategies were employed: varying injection volumes and sample dilution.
• Sixteen compounds with diverse logP values were categorized into polar and nonpolar groups.
• Three distinct workflows were derived from these strategies.

Main Results:

• All three developed workflows demonstrated successful evaluation.
• Consistent accuracy within the 80-120% range was achieved for all compound groups.
• The methods proved effective for both polar and nonpolar compounds.

Conclusions:

• The evaluated analytical strategies effectively extend the dynamic range in quantitative LC-MS/MS.
• The developed workflows provide accurate quantification across a wide range of compounds.
• These methods offer a robust solution for challenging analytical scenarios.