title: Validation of a dried blood spot method for therapeutic drug monitoring of citalopram, mirtazapine and risperidone and its active metabolite 9-hydroxyrisperidone using HPLC-MS.
abstract: Citalopram, mirtazapine and risperidone are frequently prescribed for psychiatric illnesses such as depression and psychosis or for aggressive behavior in elderly patients with dementia. The plasma concentrations vary greatly between patients, especially in elderly patients. Thus, therapeutic drug monitoring (TDM) increases the safety of antipsychotic treatment and a more rapid response to treatment may be achieved. To facilitate TDM, the objectives of this study were to develop and validate a reliable dried blood spot method to simultaneously quantify citalopram, mirtazapine and risperidone including its active metabolite 9-hydroxyrisperidone. The blood punches were extracted by methanol using an ultrasonic bath, purified by liquid-liquid extraction and analyzed by liquid chromatography/mass spectrometry (LC-MS). All acceptance criteria of the EMA and FDA guidelines for method validation were fulfilled. Linearity was shown over the range of 2.5-300μg/L for all substances. The analytes were stable for at least one month at all investigated storage conditions, including storing at room temperature exposed to light. Retrieving capillary blood by finger-pricking the assay was successfully applied in elderly patients. Venous serum samples were drawn simultaneously to compare capillary blood with serum concentrations. Given the validated results and the calculated capillary blood:serum ratio, the studied dried blood spot method offers an excellent application in TDM and can be applied in ambulatory care.
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie - Klinische Pharmazie, Westfaelische Wilhelms-Universitaet, Corrensstrasse 48, 48149 Muenster, Germany; Rundumgesund-Apotheken, Pfinztalstrasse 32, 76227 Karlsruhe, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Weber
authors.affiliation: Clemens-Wallrath-Haus, Gerontopsychiatrisches Zentrum Alexianer GmbH, Josefstrasse 4, 48151 Muenster, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Oberfeld
authors.affiliation: Clemens-Wallrath-Haus, Gerontopsychiatrisches Zentrum Alexianer GmbH, Josefstrasse 4, 48151 Muenster, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bonse
authors.affiliation: Damian-Klinik, Geriatrische Psychiatrie Alexianer GmbH, Alexianerweg 9, 48163 Muenster, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Telger
authors.affiliation: Rundumgesund-Apotheken, Pfinztalstrasse 32, 76227 Karlsruhe, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Lingg
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie - Klinische Pharmazie, Westfaelische Wilhelms-Universitaet, Corrensstrasse 48, 48149 Muenster, Germany. Electronic address: georg.hempel@uni-muenster.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D015283:Citalopram; D059788:Dried Blood Spot Testing; D016903:Drug Monitoring; D006801:Humans; D008803:Mianserin / Q000031:analogs & derivatives; D000078785:Mirtazapine; D000068882:Paliperidone Palmitate; D015203:Reproducibility of Results; D018967:Risperidone; D053719:Tandem Mass Spectrometry
chemical_list: D015283:Citalopram; D008803:Mianserin; D000078785:Mirtazapine; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: Antipsychotics; Citalopram; Dried blood spot; Mirtazapine; Risperidone; Therapeutic drug monitoring