Plasma, Oral Fluid, and Whole-Blood Distribution of Antipsychotics and Metabolites in Clinical Samples

TY - JOUR

T1 - Plasma, Oral Fluid, and Whole-Blood Distribution of Antipsychotics and Metabolites in Clinical Samples

AU - Fisher, Danielle

AU - van Schalkwyk, Gerrit I.

AU - Seedat, Soraya

AU - Curran, Sarah R.

AU - Flanagan, Bob

PY - 2013/6

Y1 - 2013/6

N2 - 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 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-2 = 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), quetia-pine (and possibly quetiapine metabolites), and risperidone/ 9-hydroxyrisperidone shows potential for oral fluid analysis.

AB - 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 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-2 = 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), quetia-pine (and possibly quetiapine metabolites), and risperidone/ 9-hydroxyrisperidone shows potential for oral fluid analysis.

KW - antipsychotics

KW - oral fluid

KW - TDM

KW - plasma:whole-blood distribution

KW - plasma:oral fluid distribution

KW - SALIVA

KW - DRUGS

KW - CHILDREN

KW - RISPERIDONE

KW - ADOLESCENTS

KW - SPECIMENS

U2 - 10.1097/FTD.0b013e318283eaf2

DO - 10.1097/FTD.0b013e318283eaf2

M3 - Article

SN - 0163-4356

VL - 35

SP - 345

EP - 351

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

IS - 3

ER -