Two fatal cases involving cardiovascular drugs diltiazem and amlodipine

Abstract

A liquid chromatographic tandem mass spectrometric method for the identification and quantification of 18 cardiovascular drugs was developed in order to evaluate two cases of fatal intoxication involving diltiazem and amlodipine respectively. Samples were simply diluted and centrifuged using a three-steps procedure with methanol, acetonitrile and mobile phase. The method proved to be selective and all the validation parameters fulfilled the acceptance criteria. In particular, linearity was studied in the range limits of quantitation (LOQ)-1,000 ng/mL (LOQ ranging from 0.8 to 33.3 ng/mL for urine and from 0.7 to 41.3 ng/mL for whole blood). The method was successfully applied to two real cases involving diltiazem and amlodipine fatal intoxications, respectively. Though the subject intoxicated by diltiazem did survive several hours after drug intake, central and peripheral blood levels at autopsy were extremely high (23.4 and 13.4 mg/L, respectively); the cause could be due to the formation of a pharmacobezoar that was found in the duodenum and that could have delayed the drug absorption. Moreover, diltiazem showed postmortem redistribution. On the contrary, the amlodipine peripheral blood level in the second case was relatively low (0.17mg/L), thus confirming that even the uncontrolled intake of a less toxic calcium channel blocker can lead to death. Furthermore, blood samples were analyzed after 2 years of storage at -20°C: both diltiazem and amlodipine showed a significant degradation (70 and 99%, respectively).