High-performance liquid chromatographic determination of diltiazem and four of its metabolites in plasma: evaluation of their stability
1988
Abstract A rapid, specific and reproducible high-performance liquid chromatographic method was developed for the simultaneous determination of diltiazem and four of its metabolites in plasma. The method involves extraction with methyl tert. -butyl ether, back-extraction into 0.017 M phosphoric acid followed by reversed-phase chromatography on a 3-μm particle, 15-cm ODS column with UV detection at 237 nm. Overall the recovery of each compound was reproducible and greater than 85%. Calibration curves were linear over the concentration range 10–250 ng/ml, with within-day or between-day coefficients of variation not exceeding 12%. A stability study indicates that while diltiazem is stable for at least six weeks in frozen plasma, more than 30% degradation of the major metabolite, N-mono-desmethyldiltiazem, was observed after four weeks at −20°C. The assay procedure has been applied to monitoring of plasma levels in patients receiving chronic oral therapy.
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