title: Identification of DP-1904 and its ester glucuronide in human urine and determination of their enantiomeric compositions by high-performance liquid chromatography with optical activity and ultraviolet detection.
abstract: The parent compound and one metabolite have been isolated from urine of five healthy male volunteers who received a single 200 mg oral dose of DP-1904. These compounds were extracted by using a Sep-Pak C18 cartridge and purified by the preparative HPLC method. On the basis of proton magnetic resonance and mass spectral data, unchanged drug and its ester glucuronide have been identified in human urine. DP-1904 has one asymmetric carbon and is used as a racemate in the current clinical trial. The enantiomeric compositions of unchanged DP-1904 and aglycon of DP-1904 glucuronide were determined by HPLC with optical activity and ultraviolet detection. The (R)-(+)-enantiomer percentages in unchanged DP-1904 and aglycon of its ester glucuronide in human urine collected at 0-4 hr after oral dosing were 60 +/- 1.3% and 38 +/- 1.4% (mean +/- SE, n = 5), respectively. The 0-4 hr urine collection represented approximately 80% of the given dose. These studies demonstrate that DP-1904 undergoes stereoselective disposition in humans. However, the difference in urinary excretion between DP-1904 enantiomers was rather small.
authors.affiliation: Drug Metabolism and Analytical Chemistry Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: H
authors.initials: H
authors.lastname: Hakusui
authors.forename: T
authors.initials: T
authors.lastname: Takegoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Kanao
mesh_terms: D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000652:urine; D006801:Humans; D007093:Imidazoles / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000652:urine*
chemical_list: D005965:Glucuronates; D007093:Imidazoles; D013764:Tetrahydronaphthalenes; C056295:nafagrel