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Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry

✍ Scribed by Michelle L. Reyzer; Yunsheng Hsieh; Kwokei Ng; Walter A. Korfmacher; Richard M. Caprioli

Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
409 KB
Volume
38
Category
Article
ISSN
1076-5174

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✦ Synopsis

Abstract

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) has been used to directly analyze and image pharmaceutical compounds in intact tissue. The anti‐tumor drug SCH 226374 was unambiguously determined in mouse tumor tissue using MALDI‐QqTOFMS (QSTAR) by monitoring the dissociation of the protonated drug at m/z 695.4 to its predominant fragment at m/z 228.1. A second drug, compound A, was detected in slices of rat brain tissue following oral administration with doses ranging from 1–25 mg/kg. Quantitation of compound A from whole brain homogenates using routine high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedures revealed that concentrations of the drug in whole brain varied from a low of 24 ng/g to a high of 1790 ng/g. The drug candidate was successfully detected by MALDI‐QqTOF in samples from each dose, covering a range of approximately two orders of magnitude. In addition, good correlation was observed between the MALDI‐QqTOFMS intensities at each dose with the HPLC/MS/MS results. Thus the MALDI‐MS response is proportional to the amount of drug in tissue. Custom software was developed to facilitate the imaging of small molecules in tissue using the MALDI‐QqTOF mass spectrometer. Images revealing the spatial localization of SCH 226374 in tumor tissue and compound A in brain tissue were acquired. Copyright © 2003 John Wiley & Sons, Ltd.

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