title: A novel method for determination of drug distribution in rat brain tissue sections by LC/MS/MS: functional tissue microanalysis.
abstract: Determination of drug distribution in brain and other tissues is important in pharmaceutical research. Tissue drug levels need to be determined routinely as they are usually diagnostic for both efficacy and toxicity. Determination of tissue levels in small organ subregions is frequently performed due to important functional considerations. These measurements have traditionally been very tedious requiring extensive dissection and specimen pooling to achieve detection of analytes of interest. Direct and indirect methods utilizing mass spectrometry have been reported for detection of analytes in tissue specimens. Typically, these require very specialized MS or sampling equipment and are only partially successful due to analyte response. We have developed a novel approach for quantitation of tissue sections called Functional Tissue Microanalysis (FTM) in which small circular samples are removed from subregions of interest, extracted and analyzed by conventional LC/MS/MS utilizing electrospray ionization. This allows direct measurement of regional concentrations without dissection and homogenization of tissue specimens as many subregions can be sampled from a single mounted section. Utilization of the FTM approach for analysis of both sagittal and coronal rat brain sections is shown for quantitation of raclopride and rimonabant. Reproducibility of this approach and comparison to conventional methods is reported.
authors.affiliation: Community of Research Excellence & Advanced Technology (CREATe), Janssen Pharmaceutical Companies of Johnson and Johnson, Welsh and McKean Roads, Spring House, PA 19477-0776, USA. jmasucci@its.jnj.com
authors.forename: John A
authors.initials: JA
authors.lastname: Masucci
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mahan
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Kwasnoski
authors.forename: Gary W
authors.initials: GW
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D008099:Liver / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000032:analysis*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations