关键词: HPLC-MS matrix effect method validation

Mesh : Calibration Chromatography, Liquid / methods standards Humans Isotope Labeling Pharmaceutical Preparations / analysis Reference Standards Reproducibility of Results Surface Properties Tandem Mass Spectrometry / methods standards

来  源:   DOI:10.3390/molecules25133047   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
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.
摘要:
近几十年来,质谱技术,特别是与高效液相色谱法等分离方法结合使用时,在制药领域变得越来越重要,生物分析,环境,和食品科学应用,因为它们具有高选择性和灵敏度。然而,由于基体效应(ME),质谱具有局限性,在复杂的混合物中可以特别标记,当分析物与其他分子共同洗脱时,定量地改变分析结果。这在方法验证期间可能是有害的,负面影响再现性,线性度选择性,准确度,和敏感性。从文学和自己的经验出发,这篇综述旨在为选择最佳操作条件以克服LC-MS技术中的基质效应提供一个简单的指南,在最短的时间内获得最佳效果。拟议的方法可以在不同的部门受益,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参数来最小化ME,色谱条件,或优化清理。相反,为了补偿ME,分析师应根据空白矩阵的可用性求助于校准方法。当空白矩阵可用时,校准可以通过同位素标记的内标和基质匹配的校准标准进行;相反,当空白矩阵不可用时,校准可以通过同位素标记的内标进行,背景减法,或代理矩阵。无论如何,MS参数的调整,色谱条件,或者清理是必要的。
公众号