RATIONALE The matrix plays an essential role in defining detection limits and ionization yields of analytes in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. Small molecule MALDI-MS analyses commonly suffer from the high background interference generated from matrices. Moreover, the inhomogeneous crystallization of some matrices, such as 2,5-dihydroxybenzoic acid (DHB), is to the detriment of the quality or repeatability of detection. We have found that N-butyl-4-hydroxy-1,8-naphthalimide (BHN) can provide improved performance as a matrix for small molecule analysis. METHODS BHN was evaluated in the low-mass region for its ionization efficiency, repeatability and background interference using O-acetyl-L-carnitine hydrochloride, Aβ35-40, Aβ35-42, and oxytocin as the model analytes. In addition, the modification effects of BHN on DHB were investigated for the in situ analysis of endogenous compounds in rat brain slices using Fourier transform ion cyclotron resonance (FTICR)-MS. RESULTS BHN is capable of ionizing small molecules, including O-acetyl-L-carnitine hydrochloride and peptides, with high repeatability and low background interference signals. A low concentration of BHN (3 mM) modifies the crystallization state of DHB but still retains its ionization performance. The determination of small molecules desorbed from tissue slices was significantly improved by using a binary matrix of DHB and BHN, yielding superior signal-to-noise ratio and signal intensities. CONCLUSIONS The new matrix BHN has exhibited suitability for the analysis of small molecules. Compared with the conventional matrices, CHCA and DHB, BHN provides a clean background in the low-mass region. In combination with DHB, the ability of BHN to form highly homogenous crystalline particles shows the clear beneficial effects of BHN for the reproducibility of MS detection.

中文翻译：

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N-丁基-4-羟基-1,8-萘二甲酰亚胺：通过基质辅助激光解吸/电离质谱分析小分子分析的新基质。

理由在基质辅助激光解吸/电离质谱（MALDI-MS）分析中，基质在定义分析物的检出限和电离产率方面起着至关重要的作用。小分子MALDI-MS分析通常会遭受基质产生的高背景干扰。此外，某些基质（例如2,5-二羟基苯甲酸（DHB））的不均匀结晶会损害检测的质量或可重复性。我们发现N-丁基-4-羟基-1,8-萘二甲酰亚胺（BHN）可以提供改进的性能，作为小分子分析的基质。方法使用O-乙酰基-L-肉碱盐酸盐，Aβ35-40，Aβ35-42和催产素作为模型分析物，在低质量区域评估BHN的电离效率，可重复性和背景干扰。此外，利用傅立叶变换离子回旋共振（FTICR）-MS技术，研究了BHN对DHB的修饰作用，用于大鼠脑片中内源性化合物的原位分析。结果BHN能够电离小分子，包括O-乙酰基-L-肉碱盐酸盐和多肽，具有高重复性和低背景干扰信号。低浓度的BHN（3 mM）会改变DHB的结晶状态，但仍保留其电离性能。通过使用DHB和BHN的二元矩阵，显着改善了从组织切片中解吸的小分子的测定，产生了优异的信噪比和信号强度。结论新型基质BHN具有适用于小分子分析的特性。与传统矩阵CHCA和DHB相比，BHN在低质量区域提供干净的背景。与DHB结合使用时，BHN形成高度均一的结晶颗粒的能力显示出BHN对于MS检测重现性的明显有益作用。