Abstract
Abstract A specific assay have been developed for the determination of dihydroquinidine (DHQ) and its major metabolites : 11-hydroxy-dihydroquinidine (11-OH DHQ), 3 (S) 3-hydroxydihydroquinidine (3-OH DHQ), dihydroquinidine 1-N-oxide (DHQ N-oxide) in human urine and plasma. The assay uses a reverse phase high performance liquid chromatographic system with fluorescence detection; the mobile phase consists of acetonitrile-acetic acid-water (7:4:89). After adding internal standard, biological samples (0.5ml) are extracted at alkaline pH by methylene chloride-iso-propanol (8:2). The organic extract is dehydrated and evaporated, the residue dissolved in 150 μl mobile phase and an aliquot injected onto the column. Lower limits of sensitivity range from 1 ng of 11-OH DHQ to 15 ng of DHQ. The standard curves are linear and results are reproducible over the concentration ranges : DHQ 0.1 to 3 μg/ml, 11-OH DHQ 2.5 to 250 ng/ml, 3-OH DHQ 10 to 1000 ng/ml and DHQ N-oxide 5 to 500 ng/ml. The assays have been tested successfully in pharmacokinetic and metabolic studies of dihydroquinidine.
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