Molecular imaging of small molecule drugs in animal tissues using laser desorption postionization mass spectrometry
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)...
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Veröffentlicht in: | Analyst (London) 2017-04, Vol.142 (7), p.1119-1124 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0003-2654 1364-5528 |
DOI: | 10.1039/c6an02721k |