LC-MS/MS Determination of 27 Antipsychotics and Metabolites in Plasma for Medication Management Monitoring

Xenobiotica. 2025 May 4:1-26. doi: 10.1080/00498254.2025.2498702. Online ahead of print.

ABSTRACT

1. With the increasing prevalence and escalating complexity of mental disorders, precise medication has become critically important. This necessitates an efficient, accurate, and convenient method for drug concentration monitoring to support laboratory personnel and clinicians. In this study, three liquid chromatography-tandem mass spectrometry methods were developed and validated for simultaneously determining and quantifying 27 antipsychotics and related metabolites in human plasma. The plasma samples were subjected to protein precipitation using methanol, with isotope-labeled internal standards, followed by separation via isocratic elution on a BEH C18 column. Mass spectrometric analysis was performed using electrospray ionization in positive ionization mode with multiple reaction monitoring for quantitative detection. The analytes demonstrated high separation efficiency, with a single sample run time of 3.0 min. The method exhibited a wide linear range with excellent linearity across the concentration range. The intra- and inter-batch precision were ≤10.00%, the accuracy was 88.67%∼113.29%. Accurate quantification of antipsychotics remained unaffected under various storage conditions: 72h at room temperature, 7d at 4 °C refrigeration, and 14d at -80 °C freezing.This validated methodology has been successfully applied to plasma samples from patients with psychiatric disorders, demonstrating its practical utility for accurate quantification of antipsychotics in large-scale and complex matrices containing multiple analytes.

PMID:40319381 | DOI:10.1080/00498254.2025.2498702