Quantitative analysis of pharmaceutical drug distribution in multiple organs by imaging mass spectrometry.
BACKGROUND
Recently, the requirement for a quantitative research method using imaging mass spectrometry (IMS) to be developed has been discussed. Specifically, the simultaneous quantification of a drug in multiple organs by using whole-body sections could be insightful for the pharmaceutical industry in the study of drug distribution.


METHODS
Frozen whole-body sections were obtained from mice injected with raclopride, a dopamine D2 receptor selective antagonist, and coated with a matrix-assisted laser desorption/ionization (MALDI) matrix compound. The whole-body sections were then analyzed using a linear ion trap mass spectrometer equipped with a MALDI source. The concentration of raclopride in each tissue was determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS).


RESULTS
The IMS-based signal intensity of raclopride strongly correlated with the concentration of the drug in the tissue samples (R=0.94; p <0.001) of six different organs. Furthermore, the spatial information obtained by IMS was very similar to that obtained by autoradiography, which is a traditional technique used for the study of drug distribution.


CONCLUSIONS
This study suggests that IMS enables the quantitative analysis of drug distribution in multiple organs simultaneously. In addition, it enhances ideal drug candidate selection in terms of efficient evaluations.
Drug Metabolism and Pharmacokinetics, Drug Developmental Research Laboratories, Shionogi & Co. Ltd., Toyonaka, Osaka, Japan. nozomi.takai@shionogi.co.jp
Nozomi
N
Takai
Yukari
Y
Tanaka
Kazuhiro
K
Inazawa
Hideo
H
Saji
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D018492:Dopamine Antagonists / Q000032:analysis / Q000493:pharmacokinetics; D006652:Histological Techniques / Q000379:methods*; D016014:Linear Models; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D020891:Raclopride / Q000032:analysis / Q000493:pharmacokinetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D014018:Tissue Distribution
D018492:Dopamine Antagonists; D020891:Raclopride