HPLC/MS findings in a fatality involving sustained-release verapamil

A fatality involving verapamil, a calcium channel blocker agent, is presented. A 51-year old male ingested 7200 mg of sustained-release (SR) verapamil at T0 and died 40 hours later of refractory, mixed shock and multiorgan failure. The symptoms displayed during hospitalization were quite typical and involved altered consciousness, hypotension, bradycardia, atrioventricular block, metabolic acidosis and renal failure. Verapamil and its primary metabolite, norverapamil, were assayed on eight plasma and two urine samples, successively taken between the admission to the ICU (T0 + 4 hours) and time of death, using an original high-performance liquid chromatography/mass spectrometry (HPLC/MS) procedure with verapamil-d3 as internal standard. Plasma verapamil and norverapamil levels on admission were 0.94 and 1.36 microg/mL, respectively, then verapamil remained practically unchanged throughout the hospitalization (0.85 microg/mL at T0 + 40 hours). The discussion focuses on the detrimental role of SR formulations in overdose, with special emphasis on the risk of pharma-cobezoar development already reported with SR-verapamil. To our knowledge, this is the first report of a verapamil fatality documented by repeated plasma measurements of the drug during the antemortem period.