A quantitation method for mass spectrometry imaging
A quantitation method for mass spectrometry imaging
复制标题
DOI：
10.1002/rcm.4891
复制
发表时间：
2011-02-01
影响因子：
2
通讯作者：
Spanton, Stephen
中科院分区：
文献类型：
--
作者：
Koeniger, Stormy L.;Talaty, Nari;Spanton, Stephen
建立了一种新的基质辅助激光解吸电离（MALDI）质谱成像定量方法。在该方法中，通过对与MSI分析的组织切片相邻的五个10 μ m组织切片进行组织均质化来确定药物浓度。通过液相色谱串联质谱法（LC/MS/MS）测定组织提取物中的药物水平。积分MSI响应与LC/MS/MS药物浓度相关，以确定每个MSI离子计数检测到的药物量。本文报告的研究评价了肝组织中的奥氮平。从接受0、1、4、8、16、30或100 mg/kg奥氮平单次给药的大鼠采集肝脏，制备含有一系列浓度的组织样品。然后通过MALDI-MSI和LC/MS/MS分析肝脏样品。确定组织浓度为300至60 000 ng/g的MALDI-MSI和LC/MS/MS相关性，并在两个数量级上产生线性关系（R-2 = 0.9792）。从这种相关性，转换因子6.3 +/-0.23 fg/离子计数用于定量MSI响应在像素水平（100 μ m）。该方法的细节，其在药物分析中的重要性，以及实施时需要考虑的问题。版权所有（C）2011约翰威利父子有限公司
A new quantitation method for mass spectrometry imaging (MSI) with matrix-assisted laser desorption/ionization (MALDI) has been developed. In this method, drug concentrations were determined by tissue homogenization of five 10 mu m tissue sections adjacent to those analyzed by MSI. Drug levels in tissue extracts were measured by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The integrated MSI response was correlated to the LC/MS/MS drug concentrations to determine the amount of drug detected per MSI ion count. The study reported here evaluates olanzapine in liver tissue. Tissue samples containing a range of concentrations were created from liver harvested from rats administered a single dose of olanzapine at 0, 1, 4, 8, 16, 30, or 100 mg/kg. The liver samples were then analyzed by MALDI-MSI and LC/MS/MS. The MALDI-MSI and LC/MS/MS correlation was determined for tissue concentrations of similar to 300 to 60 000 ng/g and yielded a linear relationship over two orders of magnitude (R-2 = 0.9792). From this correlation, a conversion factor of 6.3 +/- 0.23 fg/ion count was used to quantitate MSI responses at the pixel level (100 mu m). The details of the method, its importance in pharmaceutical analysis, and the considerations necessary when implementing it are presented. Copyright (C) 2011 John Wiley & Sons, Ltd.