High-performance liquid chromatographic determination of diltiazem and four of its metabolites in plasma: evaluation of their stability.
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-micron 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-monodesmethyldiltiazem, was observed after four weeks at -20 degrees C. The assay procedure has been applied to monitoring of plasma levels in patients receiving chronic oral therapy.
Dubé
L M
LM
Pharmaceutical Chemistry Division, Bureau of Drug Research, Banting Research Centre, Ottawa, Ontario, Canada.
Mousseau
N
N
McGilveray
I J
IJ
D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000097:blood*; D006801:Humans; D007202:Indicators and Reagents; D007475:Ion Exchange Resins; D013056:Spectrophotometry, Ultraviolet
D007202:Indicators and Reagents; D007475:Ion Exchange Resins; D004110:Diltiazem