2. Academic Validation
  3. Volumetric absorptive microsampling for the therapeutic drug monitoring of psychiatric patients treated with cariprazine

Volumetric absorptive microsampling for the therapeutic drug monitoring of psychiatric patients treated with cariprazine

  • J Pharm Biomed Anal. 2023 Nov 30:236:115740. doi: 10.1016/j.jpba.2023.115740.
Jaime Millán-Santiago 1,  Rosalba Vitagliano 2,  Fortunata Mondella 2,  Roberto Mandrioli 3,  Roccaldo Sardella 4,  Tomaž Vovk 5,  Rafael Lucena 6,  Soledad Cárdenas 6,  Federico Boaron 7,  Alessandro Serretti 8,  Carmine Petio 9,  Michele Protti 10,  Laura Mercolini 2
Affiliations

Affiliations

  • 1 Research Group of Pharmaco-Toxicological Analysis (PTA Lab), Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy; Affordable and Sustainable Sample Preparation (AS2P) Research Group, Departamento de Química Analítica, Instituto Químico para la Energía y el Medioambiente (IQUEMA), Universidad de Córdoba, Campus de Rabanales, Edificio Marie Curie, E-14071 Córdoba, Spain.
  • 2 Research Group of Pharmaco-Toxicological Analysis (PTA Lab), Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
  • 3 Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.
  • 4 Department of Pharmaceutical Sciences, University of Perugia, Via Fabretti 48, 06123 Perugia, Italy.
  • 5 Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
  • 6 Affordable and Sustainable Sample Preparation (AS2P) Research Group, Departamento de Química Analítica, Instituto Químico para la Energía y el Medioambiente (IQUEMA), Universidad de Córdoba, Campus de Rabanales, Edificio Marie Curie, E-14071 Córdoba, Spain.
  • 7 Forensic Psychiatry Unit, Department of Mental Health and Substance Abuse, AUSL of Bologna, Via Terracini 31, 40131 Bologna, Italy.
  • 8 Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Viale C. Pepoli 5, 40123 Bologna, Italy.
  • 9 Psychiatric Diagnosis and Treatment Service, AUSL of Bologna, S. Orsola - Malpighi University Hospital, Via Giuseppe Massarenti 9, 40138 Bologna, Italy.
  • 10 Research Group of Pharmaco-Toxicological Analysis (PTA Lab), Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. Electronic address: [email protected].
PMID: 37776628 DOI: 10.1016/j.jpba.2023.115740
Abstract

Psychiatric disorders are usually treated with antipsychotic agents belonging to different pharmacological and chemical classes, the most recent ones collectively known as "third-generation antipsychotics", such as cariprazine, approved in 2015 for the treatment of patients affected by schizophrenia. For these patients, a frequent therapeutic drug monitoring (TDM) becomes essential to assess compliance and to optimise and personalise their therapy, also due to cariprazine interindividual variability and narrow therapeutic range. In this study, a bioanalytical method featuring miniaturised sampling and pretreatment was developed, based on volumetric absorptive microsampling (VAMS) for TDM of psychiatric patients under cariprazine treatment and compared to a reference method based on fluid plasma analysis. Minimally invasive whole blood VAMS was coupled to an original instrumental method based on ultra-high performance liquid chromatography hyphenated to mass spectrometry (UHPLC-MS). A feasible and streamlined, yet reliable VAMS pretreatment protocol was carefully optimised and the VAMS-UHPLC-MS methodology was validated with satisfactory results in terms of linearity (r2 > 0.9970 in the 1.5-100 ng/mL range), precision (%RSD < 11.7), extraction yield (> 90.0 %) and matrix effect (8.2 ≤ %RE ≤ 10.9). Finally, the microsampling approach coupled to UHPLC-MS was successfully applied to the TDM of psychiatric patients treated with cariprazine and compared with standard fluid plasma analysis, providing reliable quali-quantitative results, and proving to be readily applicable to the clinical practice in TDM programs as a useful alternative to cariprazine plasma analysis. This is the first report of a successful microsampling application, and in particular the first report of VAMS application, for the TDM of cariprazine.

Keywords

Cariprazine; Microsampling; Therapeutic drug monitoring (TDM); Volumetric absorptive microsampling (VAMS).

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