title: Monitoring haloperidol exposure in body fluids and hair of children by liquid chromatography-high-resolution mass spectrometry.
abstract: BACKGROUND
  Haloperidol, 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone (HP), one of the most widely used antipsychotics in the treatment of schizophrenia, mania, and other psychiatric disorders, is frequently encountered in cases of unintentional pediatric intoxication because the ingestion of a small amount can cause significant toxic effects in children. For monitoring HP in suspected ingestions, a liquid chromatography-high-resolution mass spectrometry method has been developed and validated in urine, blood, and hair samples.
  
  
  METHODS
  The analyte was extracted from 1 mL blood or urine by liquid/liquid extraction and from 5 mg of hair by micropulverized extraction; gradient elution on an Atlantis T3 column was realized using HP-d4 as an internal standard. Positive ion electrospray ionization and high-resolution mass spectrometry determination were performed in an Orbitrap mass spectrometer.
  
  
  RESULTS
  The method exhibited a r > 0.999 in the studied ranges (0.1-50 ng/mL in urine and blood and 0.1-50 ng/mg in hair) and a limit of quantification of 0.1 ng/mL for urine and blood and 0.1 ng/mg for hair; intra-assay and interassay relative SDs were always more than 18%. The method was applied to determine haloperidol in 3 children who were admitted to emergency departments. HP concentrations ranged from 2 to 21 ng/mL in urine, from not detected to 4.9 ng/mL in blood, and from 0.37 to 0.73 ng/mg in hair samples.
  
  
  CONCLUSIONS
  The utilization of high-resolution/high-accuracy mass spectrometry in full scan mode allowed the identification of HP metabolites in urine and blood, thus unequivocally documenting the exposure to the drug. HP metabolites were structurally characterized by high-resolution multiple mass spectrometry. For the first time, a HP metabolite was detected in hair.
authors.affiliation: Department of Molecular Medicine, School of Medicine, University of Padova, I-35121 Padova, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Favretto
authors.forename: Giulia
authors.initials: G
authors.lastname: Stocchero
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nalesso
authors.forename: Susanna
authors.initials: S
authors.lastname: Vogliardi
authors.forename: Rafael
authors.initials: R
authors.lastname: Boscolo-Berto
authors.forename: Massimo
authors.initials: M
authors.lastname: Montisci
authors.forename: Santo D
authors.initials: SD
authors.lastname: Ferrara
mesh_terms: D001826:Body Fluids / Q000737:chemistry / Q000378:metabolism; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006197:Hair / Q000737:chemistry / Q000378:metabolism*; D006220:Haloperidol / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D007223:Infant; D008297:Male; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D006220:Haloperidol