Determination of hydroxybupropion in human serum for routine therapeutic drug monitoring in psychiatry: A tool for dose‐individualization in treatment with bupropion

Abstract

Therapeutic drug monitoring (TDM) has become a clinical routine in psychiatry. Nevertheless, for bupropion there is only one method available that is suitable for routine use. However, it involves a complex sample clean-up. Owing to the instability of bupropion in serum, the main and active metabolite hydroxybupropion was chosen as the target substance. Therefore, a simple and robust high-performance liquid chromatography method for the quantification of hydroxybupropion in serum was developed and validated. A volume of 30 μL serum was used for easy sample clean-up, based on protein precipitation with acetonitrile followed by online solid-phase extraction. As hydroxybupropion was present in high serum concentrations, UV detection was possible. Owing to the commonly available instrumentation, the method could easily be integrated in routine TDM. The newly developed method was validated following the guidelines for bioanalytical method validation of the European Medicines Agency and US Food and Drug Administration. The lower limit of quantification was 100 ng/mL (0.391 μM) and linearity was shown between 100 and 2500 ng/mL. Intraday and interday precision ranged from 1.17 to 6.79% and from 6.07 to 9.41%, respectively. Intraday and interday accuracy ranged from 89.97 to 110.86% and from 95.05 to 101.2%. The method was shown to be selective, accurate and precise. Additionally, the method was successfully implemented in the therapeutic drug monitoring laboratory of the Department of Psychiatry, Psychosomatics and Psychotherapy at the University Hospital of Würzburg, Germany. Six months of routine analysis showed a rather low correlation between applied dose and serum concentration and therefore the necessity of TDM for dose-individualization in the treatment with bupropion.

Análise da associação dos perfis de expressão gênica e das concentrações de metabólitos com a resposta ao tratamento antitabagismo

“…O novo RAM desenvolvido foi encaminhado para pedido de patente (Anexo 5) e portanto os processos para o seu desenvolvimento foram mantidos em sigilo.Os CNTs possuem uma grande área superfícial e ótima estabilidade em análise de compostos, no entanto, o material não promove a remoção de proteínas com eficiência110 115 . Os poros dos CNTs formam uma barreira física, excluindo ou permitindo a entrada de moléculas por tamanho, e os grupos hidrofílicos adicionados ao dose posológica da vareniclina é muito baixa (1mg 2 vezes ao dia, a partir do 8° dia de tratamento), em comparação com a da bupropiona (150 mg 2 vezes ao dia, a partir do 8° dia de tratamento), dessa forma, as concentrações plasmáticas de de155 (100 μg L -1 para hidroxibupropiona), apesar das concentrações de metabólitos em estado de equilíbrio em pacientes tratados com doses terapêuticas do fármaco serem bem maiores (45 -75 μg L -1 e de 500 -1500 μg L -1 ), respectivamente para bupropiona e hidroxibupropiona118 . O Quadro 6 mostra os parâmetros analíticos do presente estudo comparados com outros estudos presentes na literatura.…”