13C labelled internal standards-A solution to minimize ion suppression effects in liquid chromatography-tandem mass spectrometry analyses of drugs in biological samples?
13C labelled internal standards-A solution to minimize ion suppression effects in liquid chromatography-tandem mass spectrometry analyses of drugs in biological samples?
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DOI：
10.1016/j.chroma.2011.10.081
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发表时间：
2011-12-30
影响因子：
4.1
通讯作者：
Strand, Dag Helge
中科院分区：
文献类型：
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作者：
Berg, Thomas;Strand, Dag Helge
液相色谱-串联质谱（LC-MS/MS）由于其高选择性和灵敏度，常用于鉴定和定量人体生物样品中的药物。然而，共洗脱化合物（药物、代谢物、基质组分、杂质和降解产物）引起的离子抑制效应是一个主要问题。稳定同位素标记的内标物（SIL IS），通常是氘（H-2）标记的，通常用于补偿这些影响。在许多LC分离中，H-2标记的IS及其类似物的保留时间将不同。超高效液相色谱-串联质谱（UPLC-MS/MS）越来越多地用于生物分析。由于低于2 μ m的颗粒提供了更好的色谱分辨率，可以预期分析物与其H-2标记类似物之间的分离更大，这可能会降低SIL IS的益处。氢同位素之间的物理化学性质比其他元素的同位素之间的差异更大。与H-2标记的IS相比，C-13、N-15和O-18标记的IS与其分析物更相似，因此预期在色谱分离中的行为更相似。在这项研究中，我们已经研究了使用C-13和H-2标记的IS的测定苯丙胺和甲基苯丙胺的超高效液相色谱-MS/MS。C-13标记的IS与其分析物在不同的色谱条件下共洗脱，而H-2标记的IS与其分析物略有分离。当使用C-13标记的IS时，观察到补偿离子抑制效应的改善的能力。此外，已开发并验证了使用C-13标记的IS测定尿液中苯丙胺和甲基苯丙胺的UPLC-MS/MS方法。不幸的是，今天很少有C-13标记的IS商业可用。如果更多的C-13标记的IS成为商业可用的，它们很可能是即将到来的解决方案，以最大限度地减少生物样品中药物的LC-MS/MS分析中的离子抑制/增强效应。(C)2011 Elsevier B. V.保留所有权利。
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is frequently used to identify and quantify drugs in human biological samples due to the high selectivity and sensitivity of this technique. However, ion suppression effects caused by co-eluting compounds: drugs, metabolites, matrix components, impurities and degradation products, are a major concern. Stable isotope labelled internal standards (SIL ISs), usually deuterium (H-2) labelled, are often used to compensate for these effects. In many LC separations the retention times of H-2 labelled ISs and their analogues will differ. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is increasingly being used for bio-analysis. With the better chromatographic resolution provided with sub 2 mu m particles, larger separation between analytes and their H-2 labelled analogues can be expected, which might reduce the benefits of the SIL IS. There is a greater difference in physico-chemical properties between hydrogen isotopes than between isotopes of other elements. C-13, N-15 and O-18 labelled ISs are more similar to their analytes than H-2 labelled ISs and thereby expected to behave more similarly in chromatographic separations. In this study we have investigated the use of C-13 and H-2 labelled ISs for the determination of amphetamine and methamphetamine by UPLC-MS/MS. The C-13 labelled ISs were co eluting with their analytes under different chromatographic conditions while the H-2 labelled ISs and their analytes were slightly separated. An improved ability to compensate for ion suppression effects were observed when the C-13 labelled ISs were used. Furthermore, an UPLC-MS/MS method for determination of amphetamine and methamphetamine in urine using C-13 labelled ISs has been developed and validated. Unfortunately, there are few C-13 labelled ISs commercial available today. If more C-13 labelled ISs become commercial available they may well be the coming solution to minimize ion suppression/enhancement effects in LC-MS/MS analyses of drugs in biological samples. (C) 2011 Elsevier B.V. All rights reserved.