title: Analysis of l-DOPA-derived melanin and a novel degradation product formed under alkaline conditions.
abstract: When the therapeutic drug l-DOPA, which is used to treat Parkinson's disease, is combined with magnesium oxide (MgO), a formulation change produces a dark substance. Infrared spectroscopy reveals that this substance is melanin. After allowing the l-DOPA and MgO mixture to stand, the l-DOPA content decreases significantly, and a new degradation product (the final degradation product of l-DOPA, FDP-D) is generated. Formation of this product requires a solution with a pH of >10, and the presence of MgO is not necessary. FDP-D is not produced by tyrosinase decomposition of l-DOPA and is therefore not a melanin-related compound. Pure FDP-D is isolated by adjusting the l-DOPA solution to pH 10 with ammonium hydroxide, allowing it to stand for 3 days at room temperature, adding trifluoroacetic acid (TFA), filtering the precipitate, and separating the supernatant with high-performance liquid chromatography (HPLC). Mass spectrometry indicates that the isolated FDP-D has a molecular formula of C9H9NO7. On the basis of NMR analysis ((1)H NMR, (13)C NMR, DEPT, H-H COSY, HMQC, and HMBC), FDP-D appears to be a substance with the novel structure 7a-hydroxy-5-oxo-1,2,3,5,7,7a-hexahydropyrano [3,4-b]pyrrole-2,7-dicarboxylic acid.
authors.affiliation: Laboratory of Bioanalytical Chemistry, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; Bohsei Pharmacy, 2-1-18 Sakuradai, Isehara, Kanagawa 259-1132, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Omotani
authors.affiliation: Laboratory of Bioanalytical Chemistry, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan. Electronic address: myasuda@pharm.teikyo-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Laboratory of Bioanalytical Chemistry, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ishii
authors.affiliation: Laboratory of Bioanalytical Chemistry, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ikarashi
authors.affiliation: Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukuuchi
authors.affiliation: Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamaoka
authors.affiliation: Laboratory of Bioanalytical Chemistry, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Mawatari
authors.affiliation: Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Laboratory of Bioanalytical Chemistry, Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nakagomi
mesh_terms: D000468:Alkalies / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D007980:Levodopa / Q000032:analysis*; D008543:Melanins / Q000737:chemistry*; D013057:Spectrum Analysis
chemical_list: D000468:Alkalies; D008543:Melanins; D007980:Levodopa
keywords: Alkaline degradation; Catechol ring cleavage; MgO; NMR; l-DOPA