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

Abstract

The present study develops, refines, and validates an LC–MS/MS technique to detect haloperidol in human plasma with outstanding sensitivity (5 pg/mL), selectivity, specificity, fast analysis time, and low sample volume to enhance mental treatment regimens. Haloperidol and haloperidol D4 were tested on a Kromasil C18 stationary phase with a 35:65 ratio of 10-mM ammonium trifluoroacetate buffer to acetonitrile. A Strata-X PRO cartridge extracted the analyte and IS with improved sample extraction. ESI with multiple reaction monitoring measured haloperidol (Q1/Q3: 376.1/165.0) and D4 (Q1/Q3: 380.1/169.0). This method has high sensitivity (5.03 pg/mL), extraction efficiency (> 95%), rapid analysis (3 min), and a small sample volume (100 μL). The correction coefficient (r²) > 0.980 linearized the process from 5.03 to 6020.75 pg/mL. Nominal accuracy was 95.40%–102.52%, while intraday precision (% CV) was 0.92%–5.33%. Additionally, interday accuracy ranged from 95.40% to 102.66% and precision from 2.05% to 5.73%. This bioanalytical method for haloperidol detection in human plasma shows great sensitivity, selectivity, and linearity with an LLOQ of 5.03 pg/mL. It improves pharmacokinetics, bioequivalence, and scale-up bioavailability. Being precise, stable, and adaptable are all advantages in clinical and therapeutic monitoring.