title: The use of dried blood spots for quantification of 15 antipsychotics and 7 metabolites with ultra-high performance liquid chromatography - tandem mass spectrometry.
abstract: Therapeutic drug monitoring of antipsychotics is important in optimizing individual therapy. In psychiatric populations, classical venous blood sampling is experienced as frightening. Interest in alternative techniques, like dried blood spots (DBS), has consequently increased. A fast and easy to perform DBS method for quantification of 16 antipsychotics (amisulpride, aripiprazole, asenapine, bromperidol, clozapine, haloperidol, iloperidone, levosulpiride, lurasidone, olanzapine, paliperidone, pipamperone, quetiapine, risperidone, sertindole and zuclopenthixol) and 8 metabolites was developed. DBS were prepared using 25 μL of whole blood and extraction of complete spots was performed using methanol: methyl-t-butyl-ether (4:1). After evaporation, the extract was reconstituted in the mobile phase and 10 μL were injected on an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Separation using a C18 column and gradient elution with a flow rate of 0.5 mL/min resulted in a 6-min run-time. Ionization was performed in positive mode and a dynamic MRM method was applied. Median recovery was 66.4 % (range 28.7-84.5%). Accuracy was within the acceptance criteria, except for pipamperone (LLOQ and low concentration) and lurasidone (low concentration). Imprecision was only aberrant for lurasidone at low and medium concentration. All compounds were stable during 1 month at room temperature, 4 °C and -18 °C. Lurasidone was unstable when the extract was stored for 12 h on the autosampler. Absolute matrix effects (ME) (median 66.1%) were compensated by the use of deuterated IS (median 98.8%). The DBS method was successfully applied on 25-μL capillary DBS from patients and proved to be a reliable alternative for quantification of all antipsychotics except for olanzapine and N-desmethylolanzapine.
authors.affiliation: Toxicological Centre, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.|Laboratory for TDM and Toxicology, ZNA Stuivenberg, Lange Beeldekensstraat 267, B-2060, Antwerp, Belgium.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Patteet
authors.affiliation: Toxicological Centre, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Kristof E
authors.initials: KE
authors.lastname: Maudens
authors.affiliation: Laboratory of Toxicology, Ghent University, Harelbekestraat 72, B-9000, Ghent, Belgium.
authors.forename: Christophe P
authors.initials: CP
authors.lastname: Stove
authors.affiliation: Laboratory of Toxicology, Ghent University, Harelbekestraat 72, B-9000, Ghent, Belgium.
authors.forename: Willy E
authors.initials: WE
authors.lastname: Lambert
authors.affiliation: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Manuel
authors.initials: M
authors.lastname: Morrens
authors.affiliation: Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Sabbe
authors.affiliation: Toxicological Centre, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.|Laboratory for TDM and Toxicology, ZNA Stuivenberg, Lange Beeldekensstraat 267, B-2060, Antwerp, Belgium.
authors.forename: Hugo
authors.initials: H
authors.lastname: Neels
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D059788:Dried Blood Spot Testing; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D053719:Tandem Mass Spectrometry
chemical_list: D014150:Antipsychotic Agents
keywords: UHPLC-MS/MS; antipsychotics; dried blood spots; therapeutic drug monitoring