The use of dried blood spots for quantification of 15 antipsychotics and 7 metabolites with ultra-high performance liquid chromatography - tandem mass spectrometry

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. Copyright © 2014 John Wiley & Sons, Ltd. This article describes a UHPLC‐MS/MS method for quantification of frequently used antipsychotics and metabolites using dried blood spots. The method was extensively validated, including evaluation of the influence of the hematocrit. The method proved to be a valuable alternative to classical venous blood withdrawal and was evaluated on dried blood spot samples from psychiatric patients.