MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, P.R. China.
Analyst. 2017 Mar 27;142(7):1119-1124. doi: 10.1039/c6an02721k.
Localization and quantification of the target drug in tissues is a key indicator of efficacy in drug discovery. In contrast to established methods that require matrices and complex sample pretreatment steps, matrix-free and low cost in situ analysis of small molecule drugs by mass spectrometry (MS) remains challenging. Here, we present a novel approach, laser desorption postionization (LDPI), which is coupled to a linear time-of-flight (TOF) MS and used to image the distribution of acriflavine (ACF) directly from a histological section of mouse kidney without any matrix or sample pretreatment. The identification of the mass peaks assigned to ACF was further confirmed by DESI-MS/MS. Moreover, the matrix effect from the tissue section was explored, showing minimal desorption and ionization suppression in the LDPI-MS process. LDPI-MS imaging (LDPI-MSI) was performed on 30 μm kidney sections from mice 15 min postdose that were dosed with 30 mg kg of ACF by monitoring the fragment ion at m/z 209. The LDPI-MS image revealed a global view of the distribution of ACF in the kidney compartments (pelvis, medulla, and cortex). Estimated concentrations of ACF residue in mouse kidney were obtained by LDPI-MSI and LC-MS/MS and a 12.1% difference in measured tissue concentration was found. These results suggest that the use of LDPI-MS in small molecule drug localization and quantification directly from biological tissue at the same time is favorable.
组织中目标药物的定位和定量是药物发现中疗效的关键指标。与需要基质和复杂样品预处理步骤的既定方法相比，通过质谱（MS）对小分子药物进行无基质和低成本的原位分析仍然具有挑战性。在这里，我们提出了一种新方法，即激光解吸后电离（LDPI），它与线性飞行时间（TOF）MS 耦合，用于直接从没有任何基质或样品预处理的小鼠肾脏组织切片中对吖啶黄素（ACF）的分布进行成像。通过 DESI-MS/MS 进一步确认了分配给 ACF 的质量峰的识别。此外，还研究了来自组织切片的基质效应，显示在 LDPI-MS 过程中几乎没有解吸和离子抑制。在通过监测 m/z 209 处的碎片离子对经 30mgkg ACF 给药后 15 分钟的小鼠的 30μm 肾脏切片上进行 LDPI-MS 成像（LDPI-MSI）。LDPI-MS 图像显示了 ACF 在肾脏隔室（骨盆、髓质和皮质）中的分布的全局视图。通过 LDPI-MSI 和 LC-MS/MS 获得了小鼠肾脏中 ACF 残留的估计浓度，并发现测量的组织浓度存在 12.1%的差异。这些结果表明，在相同时间内直接从生物组织中使用 LDPI-MS 进行小分子药物定位和定量是有利的。
