title: Molecular imaging of small molecule drugs in animal tissues using laser desorption postionization mass spectrometry.
abstract: 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-1of 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.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, P.R. China. yjhu@scnu.edu.cn.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, P.R. China. yjhu@scnu.edu.cn.
authors.forename: Yongjun
authors.identifier: http://orcid.org/0000-0002-3203-5158
authors.initials: Y
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, P.R. China. yjhu@scnu.edu.cn.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Lu
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, P.R. China. yjhu@scnu.edu.cn.
authors.forename: Pengchao
authors.initials: P
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, P.R. China. yjhu@scnu.edu.cn.
authors.forename: Huaqi
authors.initials: H
authors.lastname: Zhan
mesh_terms: D000167:Acriflavine / Q000032:analysis*; D000818:Animals; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D051379:Mice; D057054:Molecular Imaging; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D000167:Acriflavine