A Novel LC-MS/MS Method for the Analysis of Antidepressants in Plasma for Clinical Research

Significance of the Topic

Depression is one of the most common psychiatric conditions globally, impacting functionality and quality of life. Reliable quantification of antidepressant drugs in plasma is critical for understanding pharmacokinetics, drug interactions and optimizing clinical research outcomes.

Objectives and Study Overview

This work describes the development and validation of a novel LC-MS/MS method capable of simultaneously measuring a panel of antidepressants in human plasma. Target analytes include citalopram, desmethylfluoxetine, duloxetine, fluoxetine, fluvoxamine, O-desmethylvenlafaxine, sertraline, venlafaxine, mirtazapine and trazodone over defined calibration ranges.

Methodology and Instrumentation

Sample Preparation:

• Plasma volume: 50 µL.
• Protein precipitation with acetonitrile containing internal standards.

Chromatographic Separation:

• Column: Waters XSelect™ Premier HSS T3.
• System: Waters ACQUITY™ UPLC™ I-Class.
• Mobile phase: water/methanol with ammonium acetate gradient.
• Run time: 5 minutes.

Detection:

• Mass spectrometer: Xevo™ TQD in tandem MS mode.

Key Results and Discussion

Method performance demonstrated:

• No carryover after high-concentration samples.
• Lower limit of quantification with precision ≤20% CV and bias ≤17.6%.
• Total precision and repeatability ≤10% RSD across pooled samples (n=25).
• Linearity with correlation coefficients ≥0.995 and acceptable back-calculated concentrations.
• Minimal matrix effects, as verified by post-column infusion and internal standard compensation.
• No significant interference from endogenous or exogenous substances.

Benefits and Practical Applications

The method offers rapid, multiplexed analysis of multiple antidepressants in a single plasma sample, facilitating high-throughput clinical research. Its robust precision and minimal matrix effects make it suitable for pharmacokinetic studies, therapeutic drug monitoring and drug–drug interaction assessments.

Future Trends and Opportunities

• Extension of the assay to additional neuropsychiatric drugs and metabolites.
• Integration with microsampling techniques to enable less invasive sampling.
• Automation and high-throughput workflows for large-scale clinical trials.
• Application of data analytics and machine learning for enhanced pharmacokinetic modeling.

Conclusion

The presented LC-MS/MS method delivers fast, accurate and reproducible quantification of a broad panel of antidepressants in plasma, supporting diverse clinical research applications.