Abstract
Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is expected to overcome some disadvantages of dried blood spots such as volume inaccuracy and influence of hematocrit (HT). This study aimed to develop and evaluate a VAMS-based strategy for quantification of 13 frequently prescribed antipsychotics in finger prick blood within the scope of adherence monitoring to complement already-established qualitative urine analysis. The final workflow consisted of VAMS tip hydration and subsequent precipitation. Samples were analyzed by using reversed-phase ultra-high-performance liquid chromatography and Orbitrap mass spectrometry operated in parallel reaction monitoring mode. The analytical procedure was successfully validated based on international recommendations at three different HT values (20%, 40%, 60%) for most of the analytes. Selectivity and within/between-run accuracy and precision were in accordance with the recommendations in most cases. Internal standard–normalized matrix factor met recommended criteria for all analytes at HT 40%. For the HT values of 20% and 60%, only four substances did not meet the criteria. Dilution integrity was given for all substances, except for olanzapine, allowing a quantification over the whole therapeutic range of selected antipsychotics. Long-term stability in VAMS tips was tested and revealed degradation of five antipsychotic drugs after 1 week of storage at 24 °C. A proof of concept of the applicability of the method was obtained by quantification of a selection of the 13 antipsychotic drugs in VAMS tips and matched plasma samples. Results were coherent between matrices. Thus, VAMS was shown to be a promising alternative for adherence monitoring of at least the investigated antipsychotics.
Highlights
A combination of antipsychotics and psychotherapy is often used to treat psychotic symptoms caused for example by schizophrenia or bipolar disorders [1, 2], but there is a wide interpatient variability concerning the response to the therapy
Assessing adherence based on serum drug concentrations to complement urine analysis is expected to be more accurate than urine analysis alone, when using the socalled dose-related concentration approach as proposed, e.g., by Ritscher et al [24]
We aimed to develop a strategy for the simultaneous quantification of the 13 most frequently prescribed antipsychotics in finger prick blood (FPB) using volumetric absorptive microsampling (VAMS) with a particular focus on adherence monitoring
Summary
A combination of antipsychotics and psychotherapy is often used to treat psychotic symptoms caused for example by schizophrenia or bipolar disorders [1, 2], but there is a wide interpatient variability concerning the response to the therapy. Venous whole blood sampling procedure can cause discomfort and anxiety, especially amongst the psychiatric population and can only be performed by trained personnel. Alternative sampling methods such as microsampling may overcome these disadvantages. The aim of this study was to develop and evaluate a VAMS-based strategy for adherence monitoring of antipsychotics in FPB by using drug concentrations to complement qualitative urine analysis [24]. The 13 most frequently prescribed antipsychotics— amisulpride, aripiprazole, cyamemazine, clozapine, haloperidol, melperone, olanzapine, paliperidone, pipamperone, promethazine, prothipendyl, quetiapine, and risperidone— should be included making the method suitable for adherence monitoring as complement to urine analysis and demonstrating its potential for TDM
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