PMID- 1349896 OWN - NLM STAT- MEDLINE DCOM- 19920615 LR - 20190629 VI - 592 IP - 1-2 DP - 1992 Feb 21 TI - Determination of the enantiomers of fenoldopam in human plasma by reversed-phase high-performance liquid chromatography after chiral derivatization. PG - 317-22 AB - Fenoldopam, a selective agonist at peripheral dopaminergic (DA-1) receptors, is administered as a racemic mixture and, consequently, an indirect stereospecific high-performance liquid chromatographic assay was developed to study the disposition of the individual enantiomers in human subjects. Fenoldopam enantiomers were extracted from alkalinized plasma into ethyl acetate prior to precolumn derivatization with the chiral reagent 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). The resulting diastereomers were separated on a reversed-phase butylsilica column and determined using triple-electrode coulometric detection. The limits of determination and detection for the S- and R-enantiomers of fenoldopam were 0.5 and 0.25 ng/ml, respectively. A linear response was observed for (S)- and (R)-fenoldopam concentrations ranging from 0.5 to 50 ng/ml in plasma. The intra-day relative standard deviations (R.S.D.s) for the plasma assay at nominal concentrations of 0.5, 5 and 50 ng/ml were 17.4, 5.2 and 6.9%, respectively, for (S)-fenoldopam and 9.9, 6.2 and 7.4%, respectively, for (R)-fenoldopam. The inter-day R.S.D.s of the method at these concentrations were 9.3, 7.7 and 7.4%, respectively, for (S)-fenoldopam and 9.5, 1.9 and 7.3%, respectively, for (R)-fenoldopam. The mean accuracy of the method at concentrations of 0.5, 5 and 50 ng/ml in plasma was found to be 106.4, 111.8 and 108.9%, respectively, for (S)-fenoldopam and 116.2, 104.2 and 111.2%, respectively, for (R)-fenoldopam. The assay developed was sufficiently sensitive, accurate and precise to support pharmacokinetic studies in human subjects. FAU - Boppana, V K AU - Boppana VK AD - Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406. FAU - Geschwindt, L AU - Geschwindt L FAU - Cyronak, M J AU - Cyronak MJ FAU - Rhodes, G AU - Rhodes G LA - eng PT - Journal Article PL - Netherlands TA - J Chromatogr JT - Journal of chromatography JID - 0427043 RN - 0 (Vasodilator Agents) RN - 67287-49-4 (2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) RN - INU8H2KAWG (Fenoldopam) SB - IM MH - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/*analogs & derivatives/blood MH - Chromatography, High Pressure Liquid/*methods MH - Fenoldopam MH - Humans MH - Male MH - Stereoisomerism MH - Vasodilator Agents/*blood EDAT- 1992/02/21 00:00 MHDA- 1992/02/21 00:01 CRDT- 1992/02/21 00:00 PHST- 1992/02/21 00:00 [pubmed] PHST- 1992/02/21 00:01 [medline] PHST- 1992/02/21 00:00 [entrez] AID - 10.1016/0021-9673(92)85102-y [doi] PST - ppublish SO - J Chromatogr. 1992 Feb 21;592(1-2):317-22. doi: 10.1016/0021-9673(92)85102-y.