Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior (CICS-UBI), Avenida Infante D. Henrique, 6200-506, Covilhã, Portugal.
Laboratório de Fármaco-Toxicologia - UBIMedical, Universidade da Beira Interior, Estrada Municipal 506, 6200-284, Covilhã, Portugal.
Anal Bioanal Chem. 2019 Sep;411(23):6141-6153. doi: 10.1007/s00216-019-02005-8. Epub 2019 Jul 10.
The present work describes the optimization and validation of an analytical method for the determination of six antipsychotic drugs (chlorpromazine, levomepromazine, cyamemazine, clozapine, haloperidol, and quetiapine) in oral fluid samples after solvent extraction from dried saliva spots, by gas chromatography coupled to tandem mass spectrometry. The method was fully validated, and the included parameters were selectivity, linearity, limits of quantification, precision and accuracy, stability, and recovery. The method was linear for all compounds from 10 to 400 ng/mL, except for haloperidol (5-100 ng/mL), presenting coefficients of determination higher than 0.99. Inter- and intra-day precision and accuracy were in conformity with the criteria usually seen in bioanalytical method validation; i.e., coefficients of variation were lower than 15% and an accuracy of 15% or better for all studied drugs. The recoveries obtained with this miniaturized technique ranged from 63 to 97%. The herein described method is the first to be reported using the dried saliva spots approach for the analysis of these antypshychotic drugs, proving great sensitivity apart from its simple and fast procedure. The method was considered a good alternative to the conventional techniques to be applied in clinical and toxicological analyses, even more taking into account the extremely low sample volume used (50 μL). Graphical abstract.
本工作描述了一种分析方法的优化和验证，该方法用于在溶剂从干燥唾液斑中提取后，通过气相色谱-串联质谱法测定口服液样品中的六种抗精神病药物（氯丙嗪、左美丙嗪、氰美嗪、氯氮平、氟哌啶醇和喹硫平）。该方法经过了全面验证，包括选择性、线性、定量限、精密度和准确度、稳定性和回收率等参数。该方法对于所有化合物均具有线性，线性范围为 10-400ng/mL，除氟哌啶醇（5-100ng/mL）外，其决定系数均高于 0.99。日内和日间精密度和准确度符合生物分析方法验证的通常标准；即，变异系数低于 15%，所有研究药物的准确度均在 15%或更好。该微型化技术的回收率范围为 63-97%。本研究方法是首次报道使用干燥唾液斑方法分析这些抗精神病药物，除了操作简单、快速外，还具有很高的灵敏度。该方法被认为是常规技术的良好替代品，可应用于临床和毒理学分析，尤其是考虑到所用的样品体积非常低（50μL）。
