Routine Therapeutic Drug Monitoring of Haloperidol in Human Serum by Liquid Chromatography-Tandem Mass Spectrometry

Abstract

Therapeutic drug monitoring (TDM) is a suitable and accepted tool for optimizing therapy with many antipsychotics. The guidelines of AGNP-TDM Expert Group strongly recommend TDM for haloperidol. We evaluated chromatographic conditions and mass spectrometry detection for its quantification in human serum to increase the number of monitored drugs in our hospital. Simple sample preparation using protein precipitation by mixture of acetonitrile-methanol (40:60, v/v) with zinc sulfate and fast gradient liquid chromatography-tandem mass spectrometry provided an effective method for the use in routine clinical settings. The separation was performed on a BEH C18 column (2.1 x 50 mm, 1.7µm) by using binary mobile phase (A: 0.1% formic acid in water, v/v; B: 0.1% formic acid in acetonitrile, v/v). Alprenolol was applied as an internal standard. Mass spectrometric detection was carried out in the positive electrospray ionization mode. The method was validated over the concentration range of 0.13–100 ng/mL with overall recovery of haloperidol 96.7 % - 100.0 %. The intra-day and inter-day precisions determined at the three concentration levels were in the range of 1.4 % to 9.7 %. Selected reaction monitoring and negligible matrix effect allow to achieve a required quantification limit. The presented method is applicable to routine therapeutic drug monitoring of haloperidol in clinical practice with a reasonable short analysis time (5 min).