title: Plasma, oral fluid, and whole-blood distribution of antipsychotics and metabolites in clinical samples.
abstract: BACKGROUND
  Oral fluid provides a noninvasive method of sample collection. The aim of this study was to obtain oral fluid, plasma, and whole blood from patients prescribed amisulpride, aripiprazole, clozapine, quetiapine, risperidone, or sulpiride and to measure plasma:whole blood and plasma:oral fluid analyte distribution.
  
  
  METHODS
  Matched oral fluid, plasma and whole-blood samples were analyzed by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  There were 101 sets of samples from 90 (56 male, 34 female) patients (nine prescribed 2 antipsychotics, and one 3). There were ≤ 5 samples for aripiprazole, amisulpride, and sulpiride. There was a good relationship between the plasma and hemolyzed whole-blood concentrations (R > 0.95), with plasma:whole-blood ratios varying between 0.7 (amisulpride) and 1.8 (aripiprazole). Amisulpride plasma and oral fluid concentrations were similar, whereas aripiprazole and dehydroaripiprazole oral fluid concentrations were approximately 8% of those in the plasma, reflecting the weak and strong plasma protein binding of these compounds, respectively. For the other analytes, plasma concentrations were 2-4 times higher than oral fluid concentrations. In general, there was a poor relationship (R = 0.3-0.7) between the plasma and oral fluid concentrations, possibly due to intrapatient saliva pH variation during sample collection.
  
  
  CONCLUSIONS
  This work shows that hemolyzed whole-blood samples can be used for therapeutic drug monitoring purposes for the analytes of interest, provided that the plasma:whole-blood ratio is taken into account when interpreting results. For aripiprazole and dehydroaripiprazole, measurements in oral fluid will probably not be feasible. However, the relationship between plasma and oral fluid concentration for amisulpride, clozapine (and norclozapine), quetiapine (and possibly quetiapine metabolites), and risperidone/9-hydroxyrisperidone shows potential for oral fluid analysis.
authors.affiliation: Toxicology Unit, Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, Denmark Hill, London, United Kingdom. danielle.fisher@nhs.net
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Fisher
authors.forename: Gerrit I
authors.initials: GI
authors.lastname: van Schalkwyk
authors.forename: Soraya
authors.initials: S
authors.lastname: Seedat
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Curran
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Flanagan
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents