One major challenge in quantifying drugs in biological matrices is to manage interfering compounds. A technique such liquid chromatography coupled to mass spectrometry in tandem (LC-MS/MS) is especially suitable for this application due to its high sensitivity and selectivity in detecting low concentrations of analytes in a complex system. Due to the complexity of LC-MS/MS systems, a number of experimental parameters must be optimized to provide an adequate separation and detection of the analyte. In the present work, a design of experiments approach was developed to optimize an LC-MS/MS-based bioanalytical method to extract olanzapine (OLZ) and quetiapine (QTP) from human plasma. Three steps for the optimization process were conducted: central composite face-centered design to optimize chromatographic parameters (Step 1), ionization in mass spectrometry (Step 2) and a full 32 factorial design to optimize analyte extraction conditions (Step 3). After the optimization process, resolutions and QTP and OLZ retention time (2.3 and 4, respectively) were optimum with pH of 4.7 and 85.5% of acetonitrile for the chromatographic step. Mass spectrometry optimization step provided an increase of (±50%) in the average peak area with high signal-to-noise relationship for the analytes studied. The proposed extraction method was 70% more efficient than the initial method for all drugs analyzed.

中文翻译：

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通过设计将质量应用于奥氮平和喹硫平LC-MS / MS生物分析。

量化生物基质中药物的主要挑战是管理干扰化合物。液相色谱-质谱联用技术（LC-MS / MS）特别适用于此应用，因为它在检测复杂系统中低浓度分析物时具有很高的灵敏度和选择性。由于LC-MS / MS系统的复杂性，必须优化许多实验参数以提供对分析物的充分分离和检测。在目前的工作中，设计了一种实验方法，以优化基于LC-MS / MS的生物分析方法，以从人血浆中提取奥氮平（OLZ）和喹硫平（QTP）。优化过程分为三个步骤：中心复合面中心设计以优化色谱参数（步骤1），质谱中的电离（步骤2）和完整的32因子设计以优化分析物提取条件（步骤3）。经过优化处理后，色谱步骤的分离度以及QTP和OLZ保留时间（分别为2.3和4）是最佳的，pH分别为4.7和85.5％的乙腈。质谱优化步骤使所研究的分析物的平均峰面积增加了（±50％），且具有高信噪比。对于所有分析的药物，拟议的提取方法比初始方法的效率高70％。质谱优化步骤使所研究的分析物的平均峰面积增加（±50％），且具有高信噪比。对于所有分析的药物，拟议的提取方法比初始方法的效率高70％。质谱优化步骤使所研究的分析物的平均峰面积增加（±50％），且具有高信噪比。对于所有分析的药物，拟议的提取方法比初始方法的效率高70％。