title: Development of a sensitive and quantitative analytical method for 1H-4-substituted imidazole histamine H3-receptor antagonists utilizing high-performance liquid chromatography and dabsyl derivatization.
abstract: A sensitive and versatile analytical method utilizing high-performance liquid chromatography (HPLC) and precolumn derivatization of 1H-4-substituted imidazole compounds is described. A HPLC method using 4-dimethylaminoazobenzene-4'-sulfonyl chloride (dabsyl chloride) and ultraviolet (UV) detection was developed for the analysis of histamine (HA) H3-selective compounds in human plasma, rat plasma, or homogenized rat cortical tissue. The average intra- and inter-assay variability, over a range of 10 to 0.01 microg/ml, was determined to be acceptable. The lower limit of detection for the dabsylated ligands was estimated to be <1.0 ng/ml while the lower limit of quantitation (LLOQ) was determined to be 10 ng/ml of conjugate. This assay has demonstrated it's suitability for the sensitive quantitation of several structurally diverse 1H-4-substituted imidazole HA H3-receptor antagonists in biological matrices for pharmacokinetic and biodistribution studies.
authors.affiliation: Gliatech, Inc., Cleveland, OH 44122, USA. mhandley@earthlink.net
authors.forename: M K
authors.initials: MK
authors.lastname: Handley
authors.forename: W W
authors.initials: WW
authors.lastname: Hirth
authors.forename: J G
authors.initials: JG
authors.lastname: Phillips
authors.forename: S M
authors.initials: SM
authors.lastname: Ali
authors.forename: A
authors.initials: A
authors.lastname: Khan
authors.forename: L
authors.initials: L
authors.lastname: Fadnis
authors.forename: C E
authors.initials: CE
authors.lastname: Tedford
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006633:Histamine Antagonists / Q000032:analysis* / Q000097:blood; D006801:Humans; D007093:Imidazoles / Q000032:analysis* / Q000097:blood; D008297:Male; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D018100:Receptors, Histamine H3; D012680:Sensitivity and Specificity; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives*
chemical_list: D006633:Histamine Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3; C010572:4-N,N-dimethylaminoazobenzene-4'-sulfonyl chloride; D004124:p-Dimethylaminoazobenzene