Overcoming ionization effects through chromatography: A case study for the ESI-LC-MS/MS quantitation of a hydrophobic therapeutic agent in human serum using a stable-label internal standard
Overcoming ionization effects through chromatography: A case study for the ESI-LC-MS/MS quantitation of a hydrophobic therapeutic agent in human serum using a stable-label internal standard
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DOI：
10.1016/j.jchromb.2009.05.031
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发表时间：
2009-07-15
影响因子：
3
通讯作者：
Wujcik, Chad E.
中科院分区：
文献类型：
--
作者：
Zhang, Guodong;Wujcik, Chad E.
在人血浆提取物中观察到疏水分析物及其稳定同位素标记内标物（SIL IS）的显著电喷雾电离效应。分析物和SIL IS在抑制区域内的保留略有偏移，导致差异抑制，导致计算浓度偏倚。六个丰富的内源性磷脂被确定为电离抑制的潜在贡献者。使用pH值（相对于分析物的log D）优化色谱条件，以更好地从分析物和SIL IS中分离附近的磷脂，并最大限度地减少电离抑制。该方法的成功验证证明了在不进一步改变提取程序的情况下研究微小色谱变化以补救有害电离效应的价值。(C)2009 Elsevier B.V.保留所有权利。
Significant electrospray ionization effects were observed for a hydrophobic analyte and its stable isotopically labeled internal standard (SIL IS) in human plasma extracts. Analyte and SIL IS were slightly offset in retention within the suppression region resulting in a differential suppression that biased calculated concentrations. Six abundant endogenous phospholipids were identified as potential contributors to ionization suppression. Chromatographic conditions were optimized using pH (relative to the log D of the analytes), to better resolve nearby phospholipids from the analyte and SIL IS and minimize ionization suppression. The successful validation of this method demonstrates the value of investigating minor chromatographic changes to remediate detrimental ionization effects without further altering extraction procedures. (C) 2009 Elsevier B.V. All rights reserved.