Calcium channel blocking agents fatal poisoning: determination of amlodipine and diltiazem by LC-MS/MS.

Introduction. Amlodipine and Diltiazem are calcium channel blocking agents used as antihypertensive. In this study we describe two fatal overdoses of these drugs. In the first case the deceased was a 45-year-old man who ingested an unknown number of amlodipine tablets. In the second case the deceased was a 38 year-old woman who ingested an unspecified amount of diltiazem tablets. Both cases were classified as suicide. Methods. Postmortem analysis were performed by LC-MS/MS on blood, urine, bile and stomach contents. Calibration curves were prepared in blood, urine and bile. Mefenamic acid was used as internal standard, samples were diluted 1:1 with methanol and ten microliters were injected into the LC-MS/MS system. Results. Amlodipine concentrations were 173 ng/ml in femoral blood, 128 ng/ml in urine and 5,150 ng/ml in bile. Diltiazem levels were 17.4 g/ml in femoral blood, 28.2 g/ml in cardiac blood, 4.5 g/ml in urine and 72.7 g/ml in bile. Amlodipine and Diltiazem were still identified in gastric contents. In both cases the concentrations of these drugs found in urine were lower than in blood samples. Conclusions. We have developed a simple and reliable method to determine this class of drugs in biological samples. The concentration of Amlodipine in blood sample was very low if compared with earlier reported cases; on the contrary as regards Diltiazem, concentrations in body fluids were very high, and the heart/femoral blood ratio was 1.62. In both cases autopsy did not show any signs of disease and Amlodipine and Diltiazem were the only drugs found in toxic levels in blood.