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Journal of chromatography. B, Biomedical sciences and applications

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.


PMID 9824237

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.

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