Schizophrenia is one of the most frequent psychiatric disorders, affecting about 1% of the world global population. The first antipsychotic class, the so-called “classical neuroleptics”, includes agents such as Chlorpromazine, Fluphenazine and Haloperidol. These drugs are only active against positive symptoms of psychoses and tend to cause frequent and severe side effects such as extra-pyramidal syndrome, tardive dyskinesia and hyperprolactinemia. The introduction of “atypical antipsychotics“ such as Clozapine, Risperidone and Ziprasidone has allowed the treatment of schizophrenia negative symptoms as well and a reduction in the incidence and severity of side effects. However, there are some patients which are “non responder” to the therapy with atypical antipsychotics, thus classical neuroleptics are still widely used, sometimes even under polypharmacy with atypical antipsychotics. Due to the complexity of schizophrenia pharmacological treatment, therapy personalization is advisable to obtain a satisfactory symptom control. Therapeutic Drug Monitoring (TDM) is one of the most important tools to personalize and optimize psychiatric therapy, dealing with drug plasma level determination, correlation of plasma levels with administered doses and correlation of therapeutic effects with side effects. Aim of this study is the development of an innovative and reliable analytical methodology for the simultaneous determination of classical and atypical antipsychotics in blood. A novel blood sampling and pre-treatnrent approach is presented herein, based on Dried Blood Spot (DBS) testing, coupled to a fast and sensitive liquid chromatography - mass spectrometry method (LC-MS/MS). The preliminary results are very promising and assays are currently in progress to fully validate the method in terms of linearity, precision and accuracy and to apply it to the TDM of several schizophrenic patients treated with classical neuroleptics and/or atypical antipsychotics.

An innovative analytical methodology for the Therapeutic Drug Monitoring (TDM) of schizophrenic patients: Dried Blood Spots (DBS)

MANDRIOLI, ROBERTO;SORELLA, VITTORIO;RAGGI, MARIA AUGUSTA
2012

Abstract

Schizophrenia is one of the most frequent psychiatric disorders, affecting about 1% of the world global population. The first antipsychotic class, the so-called “classical neuroleptics”, includes agents such as Chlorpromazine, Fluphenazine and Haloperidol. These drugs are only active against positive symptoms of psychoses and tend to cause frequent and severe side effects such as extra-pyramidal syndrome, tardive dyskinesia and hyperprolactinemia. The introduction of “atypical antipsychotics“ such as Clozapine, Risperidone and Ziprasidone has allowed the treatment of schizophrenia negative symptoms as well and a reduction in the incidence and severity of side effects. However, there are some patients which are “non responder” to the therapy with atypical antipsychotics, thus classical neuroleptics are still widely used, sometimes even under polypharmacy with atypical antipsychotics. Due to the complexity of schizophrenia pharmacological treatment, therapy personalization is advisable to obtain a satisfactory symptom control. Therapeutic Drug Monitoring (TDM) is one of the most important tools to personalize and optimize psychiatric therapy, dealing with drug plasma level determination, correlation of plasma levels with administered doses and correlation of therapeutic effects with side effects. Aim of this study is the development of an innovative and reliable analytical methodology for the simultaneous determination of classical and atypical antipsychotics in blood. A novel blood sampling and pre-treatnrent approach is presented herein, based on Dried Blood Spot (DBS) testing, coupled to a fast and sensitive liquid chromatography - mass spectrometry method (LC-MS/MS). The preliminary results are very promising and assays are currently in progress to fully validate the method in terms of linearity, precision and accuracy and to apply it to the TDM of several schizophrenic patients treated with classical neuroleptics and/or atypical antipsychotics.
Proceedings of the 21st National Meeting on Medicinal Chemistry (NMMC 2012)
58
58
Laura Mercolini; Roberto Mandrioli; Vittorio Sorella; Maria Augusta Raggi
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/150054
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