title: A gradient HPLC test procedure for the determination of impurities and the synthetic precursors in 2-[4-(1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl)-phenyl]-2-methylpropionic acid.
abstract: A gradient high-performance liquid chromatographic (HPLC) test procedure is developed and evaluated for its ability to establish the levels of impurities and remaining synthetic precursors in 2-[4-(1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl)-phenyl]-2-methylpropionic acid. A gradient program with a mobile phase of 0.02 M sodium phosphate buffer and 0.004 M sodium perchlorate in acetonitrile-water (approximately pH 2.5) is used with a Spherisorb C6 column. The acetonitrile composition is increased linearly from 40% to 65% over a 45-min period and held at 65% for 20 min. UV detection at 210 nm is used to quantitate all components. The procedure is validated for accuracy using spiked levels (0.1% to 1.5%, w/w) with two suspected impurities, the synthetic precursors. A multiday repeatability study using two different Spherisorb C6 columns and HPLC systems shows consistent impurity quantitation results with one production lot of the bulk compound.
authors.affiliation: University of Cincinnati, Mail Location 0172, Cincinnati, OH 45221-0172, USA. bhymer@hotmail.com
authors.forename: C
authors.initials: C
authors.lastname: B'Hymer
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D010666:Phenylpropionates / Q000032:analysis*; D010880:Piperidines / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
chemical_list: C523191:2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)butyl)phenyl)-2-methylpropionic acid; D010666:Phenylpropionates; D010880:Piperidines