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

Millán-Santiago, Jaime (author), Vitagliano, Rosalba (author), Mondella, Fortunata (author), Mandrioli, Roberto (author), Sardella, Roccaldo (author), Vovk, Tomaž (author), Lucena, Rafael (author), Cárdenas, Soledad (author), Boaron, Federico (author), Mercolini, Laura (author)

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 classic, 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 ($r^2$ > 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.

• Language: English
• Keywords: cariprazine, microsampling, therapeutic drug monitoring (TDM), volumetric absorptive microsampling (VAMS), microsampling (VAMS)
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: Str. 1-7
• Numbering: Vol. 236, art. 115740
• PID: 20.500.12556/RUL-151577
• UDC: 615.214:616.89
• ISSN on article: 0731-7085
• DOI: 10.1016/j.jpba.2023.115740
• COBISS.SI-ID: 165592835
• Publication date in RUL: 10.10.2023

Record is a part of a journal

• Title: Journal of pharmaceutical and biomedical analysis
• Shortened title: J. pharm. biomed. anal.
• Publisher: Elsevier B.V.
• ISSN: 0731-7085
• COBISS.SI-ID: 6557447

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: kariprazin, mikrovzorčenje, terapevtsko spremljanje zdravil, volumetrično absorpcijsko mikrovzorčenje, antipsihotiki, psihiatrija

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Spanish Ministry of Science and Innovation
• Project number: PID2020-112862RB-I00

• Funder: Other - Other funder or multiple funders
• Funding programme: Spanish Ministry of Science, Innovation and Universities
• Project number: FPU19/01488