STABILITY OF DILTIAZEM AND ITS METABOLITES IN HUMAN BLOOD-SAMPLES

The stability of diltiazem and its metabolites in blood samples from patients under chronic diltiazem therapy was investigated. When whole blood was kept for 1 h at room temperature between sampling and centrifugation, the concentration of N-demethyldiltiazem (MA) decreased significantly, with an average loss of 24%. Under the same conditions, an average loss of 14% of diltiazem occurred, whereas the concentrations of the metabolites deacetyldiltiazem and N-demethyldeacetyldiltiazem did not change significantly. No significant decrease in MA and diltiazem concentrations was observed when whole blood was stored for 1 h in an ice bath. In spiked plasma samples kept at room temperature, only MA was unstable, with an average loss of 13% after 4 h. The present study shows the importance of observing rigorous conditions for the transport and treatment of blood samples. To achieve accurate determination of diltiazem and related compounds, the blood must be centrifuged immediately after collection or kept on ice for up to 1 h. The plasma samples must be immediately frozen at -80-degrees-C and can be stored for up to 5 weeks before analysis. Using these rigorous conditions, we observed that MA is the main metabolite of diltiazem in plasma from patients under chronic oral diltiazem therapy.