In recent decades, mass spectrometry techniques, particularly when combined with separation methods such as high-performance liquid chromatography, have become increasingly important in pharmaceutical, bio-analytical, environmental, and food science applications because they afford high selectivity and sensitivity. However, mass spectrometry has limitations due to the matrix effects (ME), which can be particularly marked in complex mixes, when the analyte co-elutes together with other molecules, altering analysis results quantitatively. This may be detrimental during method validation, negatively affecting reproducibility, linearity, selectivity, accuracy, and sensitivity. Starting from literature and own experience, this review intends to provide a simple guideline for selecting the best operative conditions to overcome matrix effects in LC-MS techniques, to obtain the best result in the shortest time. The proposed methodology can be of benefit in different sectors, such as pharmaceutical, bio-analytical, environmental, and food sciences. Depending on the required sensitivity, analysts may minimize or compensate for ME. When sensitivity is crucial, analysis must try to minimize ME by adjusting MS parameters, chromatographic conditions, or optimizing clean-up. On the contrary, to compensate for ME analysts should have recourse to calibration approaches depending on the availability of blank matrix. When blank matrices are available, calibration can occur through isotope labeled internal standards and matrix matched calibration standards; conversely, when blank matrices are not available, calibration can be performed through isotope labeled internal standards, background subtraction, or surrogate matrices. In any case, an adjusting of MS parameters, chromatographic conditions, or a clean-up are necessary.

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补偿或最小化矩阵效应？克服液相色谱-质谱技术中基质效应的策略：教程回顾

近几十年来，质谱技术，尤其是与高效液相色谱等分离方法结合使用时，在制药、生物分析、环境和食品科学应用中变得越来越重要，因为它们具有高选择性和灵敏度。然而，质谱法由于基质效应 (ME) 存在局限性，当分析物与其他分子一起洗脱时，基质效应 (ME) 在复杂混合物中尤为明显，从而定量地改变分析结果。这在方法验证期间可能是有害的，对重现性、线性、选择性、准确度和灵敏度产生负面影响。从文学和自己的经验出发，本综述旨在提供一个简单的指南，用于选择最佳操作条件以克服 LC-MS 技术中的基质效应，从而在最短的时间内获得最佳结果。所提出的方法可以在不同的领域受益，例如制药、生物分析、环境和食品科学。根据所需的灵敏度，分析师可能会最小化或补偿 ME。当灵敏度至关重要时，分析必须尝试通过调整 MS 参数、色谱条件或优化净化来最小化 ME。相反，为了补偿 ME，分析人员应根据空白基质的可用性采用校准方法。当空白基质可用时，可以通过同位素标记的内标和基质匹配的校准标准进行校准；反过来，当空白基质不可用时，可以通过同位素标记的内标、背景扣除或替代基质进行校准。在任何情况下，都需要调整 MS 参数、色谱条件或净化。