title: Simultaneous determination of diastereoisomeric and enantiomeric impurities in (1R, 3R)-1-(1,3-benzodioxol-5-yl)-2-(chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester a key intermediate of tadalafil by chiral high-performance liquid chromatography.
abstract: (1R, 3R)-1-(1, 3-Benzodioxol-5-yl)-2-(chloroacetyl)-2, 3, 4, 9-tetrahydro-1H-pyrido[3, 4-b]indole-3-carboxylic acid methyl ester ((1R, 3R)-Cpe) is a key intermediate used in the synthesis of tadalafil, a highly selective phosphodiesterase type-5 inhibitor. In the present study, a chiral high-performance liquid chromatography method was developed for the simultaneous determination of diastereoisomeric and enantiomeric impurities in (1R, 3R)-Cpe. Separation was performed on an Ultron ES-OVM chiral column (150 mm × 4.6 mm, 5 μm,) with a guard column at a column temperature of 30°C. The gradient elution used was acetonitrile (solvent A) and water (solvent B), and the following elution program was used at a flow rate of 1 ml/min: 0-5 min (80% B), 5-10 min (80-60% B), 10-12 min (60% B). The detection wavelength was 220 nm. The four isomers of Cpe were baseline separated in 12 min. The results of method validation indicated that the method was specific and sensitive and was suitable for the quality control of diastereoisomeric and enantiomeric impurities in (1R, 3R)-Cpe.
authors.affiliation: Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Lushan
authors.initials: L
authors.lastname: Yu
authors.forename: Yiping
authors.initials: Y
authors.lastname: Jin
authors.lastname: Jianzhou
authors.forename: Chun
authors.initials: C
authors.lastname: Ye
authors.forename: Jinzhao
authors.initials: J
authors.lastname: Wang
authors.forename: Gongyun
authors.initials: G
authors.lastname: Hu
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D002243:Carbolines / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007211:Indoles / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification*; D016014:Linear Models; D058986:Phosphodiesterase 5 Inhibitors / Q000138:chemical synthesis*; D011725:Pyridines / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification*; D013237:Stereoisomerism; D000068581:Tadalafil; D013997:Time Factors
chemical_list: D002243:Carbolines; D002264:Carboxylic Acids; D007211:Indoles; D058986:Phosphodiesterase 5 Inhibitors; D011725:Pyridines; C574474:(1R,3R)-1-(1,3-benzodioxol-5-yl)-2-(chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido(3,4-b)indole-3-carboxylic acid methyl ester; D000068581:Tadalafil