Highly Analytically-sensitive Analysis of Aldosterone in Plasma on the Xevo TQ-XS for Clinical Research

Importance of the Topic

Aldosterone is a key mineralocorticoid steroid hormone, critically involved in fluid balance and blood pressure regulation. Measuring its low-level concentrations in plasma (<25 pg/mL) is essential in pharmacological studies of aldosterone synthase inhibitors, yet traditional assays often lack sufficient sensitivity and precision.

Study Objectives and Overview

This study compared the analytical performance of the Waters Xevo TQ-XS tandem quadrupole mass spectrometer with its predecessor, the Xevo TQ-S, focusing on sensitivity and imprecision in quantifying aldosterone at trace levels relevant to clinical research.

Methodology and Instrumentation

Plasma samples were precipitated using zinc sulfate/methanol and diluted with phosphoric acid before solid-phase extraction on an Oasis MAX µElution Plate. Following sequential washes with phosphoric acid, ammonia in methanol, and water, analytes were eluted with aqueous methanol and diluted for injection. Chromatographic separation was performed on an ACQUITY UPLC I-Class system with a CORTECS C18 column under a water/methanol gradient. MRM transitions monitored were 359.2>189.0 (quantifier) and 359.2>297.2 (qualifier), with aldosterone-4H2 as an internal standard (363.2>190.0). Concentrations reported in pg/mL were converted to pmol/L using a factor of 2.774.

Used Instrumentation

• Waters Xevo TQ-XS tandem quadrupole mass spectrometer with StepWave XS ion optics and Xtended Dynamic Range Detector
• Waters Xevo TQ-S tandem quadrupole mass spectrometer (for comparison)
• ACQUITY UPLC I-Class system
• CORTECS C18 column
• Oasis MAX µElution Plate

Main Results and Discussion

The Xevo TQ-XS demonstrated a substantial sensitivity gain and improved reproducibility:

• At 1 pg/mL standard (50 fg on column), the TQ-XS achieved a signal-to-noise ratio of 54 versus 9 on the TQ-S, with <2% RSD compared to 20.5% RSD.
• Low calibrator in stripped serum (15 pg/mL) exhibited enhanced peak response and reproducibility over three days.
• Endogenous aldosterone in plasma (11.6 pg/mL, 350 fg on column) produced clearer chromatographic peaks on the TQ-XS.
• Total imprecision across four QC levels (21–669 pg/mL, n=30) improved on the TQ-XS (3.9–7.9% CV) versus the TQ-S (5.4–8.3% CV).

Benefits and Practical Applications

• Detection of aldosterone down to 1 pg/mL with high signal-to-noise ratios supports reliable quantification in clinical research.
• Improved imprecision (<8% CV) across a broad concentration range enhances data quality and study robustness.
• Expanded dynamic range and robust performance facilitate method transfer and streamline high-throughput analysis workflows.

Future Trends and Opportunities

Ongoing advancements in ion transfer optics and detector technologies are expected to further push the limits of sensitivity and reliability. Future research may explore multiplexed steroid panels, automated sample preparation integration, and translation of these high-sensitivity methods into regulated clinical diagnostics. Enhancements in dynamic range and multiplexing will support simultaneous profiling of multiple low-abundance biomarkers.

Conclusion

The Waters Xevo TQ-XS tandem quadrupole mass spectrometer significantly outperforms its predecessor in the analysis of aldosterone in plasma, offering superior sensitivity, precision, and dynamic range. This performance empowers more accurate quantification of low-level aldosterone, advancing clinical research in mineralocorticoid physiology and drug development.