Pioneering Human Plasma Detection of Haloperidol With 5-pg/mL Sensitivity via Refined Sample Preparation and Advanced...

Area of Science:

• Analytical Chemistry
• Bioanalysis
• Pharmacology

Background:

• Accurate quantification of antipsychotic drugs like haloperidol is crucial for effective mental health treatment.
• Existing methods may lack the sensitivity, speed, or sample volume efficiency required for optimal clinical and therapeutic monitoring.
• Advancements in bioanalytical techniques are needed to improve pharmacokinetic and bioequivalence studies.

Purpose of the Study:

• To develop, refine, and validate a highly sensitive and selective LC-MS/MS method for quantifying haloperidol in human plasma.
• To establish a rapid and efficient bioanalytical technique suitable for clinical and therapeutic drug monitoring.
• To support pharmacokinetic, bioequivalence, and bioavailability studies of haloperidol.

Main Methods:

• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) utilizing a Kromasil C18 stationary phase.
• Solid-phase extraction using a Strata-X PRO cartridge for analyte and internal standard isolation.
• Electrospray ionization (ESI) with multiple reaction monitoring (MRM) for sensitive detection.

Main Results:

• Achieved outstanding sensitivity with a lower limit of quantification (LLOQ) of 5.03 pg/mL.
• Demonstrated high extraction efficiency (>95%) and rapid analysis time (3 minutes).
• Exhibited excellent linearity (r² > 0.980), accuracy (95.40%-102.52%), and precision (intraday CV 0.92%-5.33%; interday CV 2.05%-5.73%).

Conclusions:

• The validated LC-MS/MS method provides a sensitive, selective, and rapid means for haloperidol detection in human plasma.
• This method is suitable for improving pharmacokinetic, bioequivalence, and bioavailability assessments.
• The technique's precision, stability, and adaptability offer significant advantages for clinical and therapeutic monitoring of haloperidol treatment.