Suicide with oral midazolam: Postmortem toxicological investigations using Ostro® Plate and ultra-high performance liquid chromatography coupled to tandem mass spectrometry

Abstract

A middle-aged woman was found dead with multiple empty blisters of midazolam (DORMICUM®), equivalent to 450mg, near her body. The autopsy revealed that the cause of death was secondary to an asphyxia syndrome. Standard toxicological procedures identified midazolam only in blood, urine and gastric content. A quantitative analytical method for midazolam (MDZ) and 1-hydroxy-midazolam (1-OH-MDZ) was validated using protein precipitation, a phospholipid removal Ostro® plates and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). MDZ and 1-OH-MDZ were quantified in peripheral blood at 910 ng/mL and 534 ng/mL, respectively, and superior to 2000 ng/mL in urine. Reported to the body weight, the dose, which was lethal, was estimated to 6.7 mg/kg. The usual dose used in intensive care unit is 0.03-0.3 mg/kg. MDZ intoxication outside of hospital are rare given the restricted availably of this drug in France. Nevertheless, MDZ under oral form remains available in several countries. Toxic MDZ blood concentrations are described after intravenous administration for anesthesia and are not suited for oral intoxication. Based on the autopsy findings, police investigation and toxicology results, the cause of death was determined to be a self-inflicted oral MDZ acute intoxication, which is the first to be documented to the best of our knowledge. This fatal intoxication provides analytical data that could support subsequent toxicological result interpretation in similar forensic cases.