title: A new combination MALDI matrix for small molecule analysis: application to imaging mass spectrometry for drugs and metabolites.
abstract: Since the development of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, this procedure has been specifically used for analyzing proteins or high molecular weight compounds because of the interference of matrix signals in the regions of the low mass range. Recently, scientists have been using a wide range of chemical compounds as matrices that ionize small molecules in a mass spectrometer and overcome the limitations of MALDI mass spectrometry. In this study, we developed a new combination matrix of 3-hydroxycoumarin (3-HC) and 6-aza-2-thiothymine (ATT), which is capable of ionizing small molecules, including drugs and single amino acids. In addition to ionization of small molecules, the combination matrix by itself gives less signals in the low mass region and can be used for performing imaging mass spectrometry (IMS) experiments on tissues, which confirms the vacuum stability of the matrix inside a MALDI chamber. The drug donepezil was mapped in the intact tissue slices of mice simultaneously with a spatial resolution of 150 μm during IMS. IMS analysis clearly showed that intact donepezil was concentrated in the cortical region of the brain at 60 min after oral administration. Our observations and results indicate that the new combination matrix can be used for analyzing small molecules in complex samples using MALDI mass spectrometry.
authors.affiliation: Department of Molecular Biotechnology, WCU program, Konkuk University, Seoul, 143-701, Korea.
authors.forename: Selina Rahman
authors.initials: SR
authors.lastname: Shanta
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Hong
authors.forename: Jeong Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Kyun-Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Kim
authors.forename: Sang Kyung
authors.initials: SK
authors.lastname: Kim
authors.forename: Kwang Pyo
authors.initials: KP
authors.lastname: Kim
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D000077265:Donepezil; D007189:Indans / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D007189:Indans; D010880:Piperidines; D000077265:Donepezil