Clozapine is one of the most widely used second-generation antipsychotic drugs (SGAs) for the treatment of schizophrenia. Despite advantages over first-generation drugs, clozapine still shows significant side effects and interindividual variations in efficacy. In order to ensure frequent therapeutic drug monitoring (TDM) and improve the compliance of psychiatric patients undergoing clozapine treatment, two novel dried microsampling approaches based on whole blood and plasma volumetric absorptive microsampling (b-VAMS and p-VAMS) and microfluidic generated-dried blood spot technology (mfDBS) were developed and coupled to HPLC with electrochemical detection (ED). The proposed miniaturized strategies by means of VAMS and microfluidic channel-based devices provide several advantages in terms of collection, storage, and handling compared to classical blood and plasma processing. Satisfactory validation results were obtained for all microsampling platforms, with mean extraction yields >85.1%, precision as relative standard deviation (RSD) < 5.1%, and stability < 4.5% analyte loss after 30 days for p-VAMS; mean extraction yields > 83.4%, precision RSD < 5.4%, and stability < 4.6% analyte loss after 30 days for b-VAMS, and mean extraction yields > 74.0%, precision RSD < 5.6%, and stability < 4.9% analyte loss after 30 days for mfDBS. The original microsampling methodologies have been successfully applied to the blood and plasma collected from five psychiatric patients for the monitoring of the levels of clozapine and its main metabolites, providing robust and reliable quali-quantitative results. Comparisons between results of the two dried microsampling technologies with those obtained by classic fluid plasma analysis were in good agreement and have demonstrated that the proposed miniaturized approaches could be suitable for TDM purposes.

Dried Volumetric Microsampling Approaches for the Therapeutic Drug Monitoring of Psychiatric Patients Undergoing Clozapine Treatment / Marasca, Camilla; Mandrioli, Roberto; Sardella, Roccaldo; Vovk, Tomaž; Armirotti, Andrea; Cavalli, Andrea; Serretti, Alessandro; Protti, Michele; Mercolini, Laura. - In: FRONTIERS IN PSYCHIATRY. - ISSN 1664-0640. - ELETTRONICO. - 13:(2022), pp. 794609.1-794609.11. [10.3389/fpsyt.2022.794609]

Dried Volumetric Microsampling Approaches for the Therapeutic Drug Monitoring of Psychiatric Patients Undergoing Clozapine Treatment

Marasca, Camilla
Primo
Membro del Collaboration Group
;
Mandrioli, Roberto
Secondo
Membro del Collaboration Group
;
Cavalli, Andrea
Membro del Collaboration Group
;
Serretti, Alessandro
Membro del Collaboration Group
;
Protti, Michele
Penultimo
Membro del Collaboration Group
;
Mercolini, Laura
Ultimo
Membro del Collaboration Group
2022

Abstract

Clozapine is one of the most widely used second-generation antipsychotic drugs (SGAs) for the treatment of schizophrenia. Despite advantages over first-generation drugs, clozapine still shows significant side effects and interindividual variations in efficacy. In order to ensure frequent therapeutic drug monitoring (TDM) and improve the compliance of psychiatric patients undergoing clozapine treatment, two novel dried microsampling approaches based on whole blood and plasma volumetric absorptive microsampling (b-VAMS and p-VAMS) and microfluidic generated-dried blood spot technology (mfDBS) were developed and coupled to HPLC with electrochemical detection (ED). The proposed miniaturized strategies by means of VAMS and microfluidic channel-based devices provide several advantages in terms of collection, storage, and handling compared to classical blood and plasma processing. Satisfactory validation results were obtained for all microsampling platforms, with mean extraction yields >85.1%, precision as relative standard deviation (RSD) < 5.1%, and stability < 4.5% analyte loss after 30 days for p-VAMS; mean extraction yields > 83.4%, precision RSD < 5.4%, and stability < 4.6% analyte loss after 30 days for b-VAMS, and mean extraction yields > 74.0%, precision RSD < 5.6%, and stability < 4.9% analyte loss after 30 days for mfDBS. The original microsampling methodologies have been successfully applied to the blood and plasma collected from five psychiatric patients for the monitoring of the levels of clozapine and its main metabolites, providing robust and reliable quali-quantitative results. Comparisons between results of the two dried microsampling technologies with those obtained by classic fluid plasma analysis were in good agreement and have demonstrated that the proposed miniaturized approaches could be suitable for TDM purposes.
2022
Dried Volumetric Microsampling Approaches for the Therapeutic Drug Monitoring of Psychiatric Patients Undergoing Clozapine Treatment / Marasca, Camilla; Mandrioli, Roberto; Sardella, Roccaldo; Vovk, Tomaž; Armirotti, Andrea; Cavalli, Andrea; Serretti, Alessandro; Protti, Michele; Mercolini, Laura. - In: FRONTIERS IN PSYCHIATRY. - ISSN 1664-0640. - ELETTRONICO. - 13:(2022), pp. 794609.1-794609.11. [10.3389/fpsyt.2022.794609]
Marasca, Camilla; Mandrioli, Roberto; Sardella, Roccaldo; Vovk, Tomaž; Armirotti, Andrea; Cavalli, Andrea; Serretti, Alessandro; Protti, Michele; Mercolini, Laura
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/893547
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