title: Distribution Analysis via Mass Spectrometry Imaging of Ephedrine in the Lungs of Rats Orally Administered the Japanese Kampo Medicine Maoto.
abstract: Maoto, a traditional Japanese Kampo medicine, has been used to treat various respiratory diseases, including respiratory infections and influenza. Ephedrine (EPD), the main ingredient in maoto, is also clinically used to treat respiratory diseases. However, the pharmacokinetics and distribution of EPD in the lungs after the administration of maoto have not been demonstrated. This study aimed to determine the concentrations, distribution, and pharmacokinetics of EPD and its precursor methylephedrine (MEPD) in the lungs of rats orally administered maoto (1 and 4 g/kg). We used liquid chromatography-electrospray ionization-tandem mass spectrometry to measure the ingredient concentrations. Both ingredients were detected in maoto-treated lung homogenates. Next, we examined the distribution of both ingredients in lung sections by using matrix-assisted laser desorption/ionization-mass spectrometry imaging, a powerful tool for the visualization of the distribution of biological molecules. The mass spectrometry imaging analysis detected only EPD and provided the first visual demonstration that EPD is distributed in the alveoli, bronchi, and bronchioles in the lungs of rats orally administered maoto (4 g/kg, three times at 2-h intervals). These results suggest that the pharmacological efficacy of maoto for the amelioration of respiratory symptoms is related to the distribution of EPD in the lung.
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., Ibaraki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., Ibaraki, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kushida
authors.affiliation: Department of Cellular &Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.|International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Oyama
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., Ibaraki, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Watanabe
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura &Co., Ibaraki, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
authors.affiliation: Department of Cellular &Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.|International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D007564:Japan; D008168:Lung / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D020835:Medicine, Kampo; D010936:Plant Extracts / Q000737:chemistry; D017207:Rats, Sprague-Dawley
chemical_list: D010936:Plant Extracts; C041707:N-methylephedrine; D004809:Ephedrine