Application of LC-MS Analysis to a Colchicine Fatality

A 73-year-old man developed nausea, vomiting, and diarrhea 20-30 min after receiving a 1.0 mg intravenous dose of colchicine for the treatment of severe pain due to gouty arthritis in his physician's office. He was hospitalized 8 h later, and his condition deteriorated as he developed renal and respiratory failure. He subsequently died 10 h later, or a total of 18 h after he received the original 1 mg colchicine injection. The patient received a prescription for oral 0.6 mg colchicine tablets 8 days previously and consumed eight tablets during that period, an average of 0.6 mg/day (42 of 50 tablets remained at the time of death). Colchicine concentrations were measured by liquid chromatography-mass spectrometry in selected ion monitoring mode using positive ionization. Chromatography was performed using an Eclipse XDB C8 analytical column (30 mm × 2.1-mm i.d., 3-µm particle size) and a programmed mobile phase consisting of 50mM pH 4 ammonium acetate buffer and acetonitrile. Colchicine concentrations were as follows: 50 µg/L in cardiac blood, 10 µg/L in vitreous humor, 575 µg/kg in liver, 12,000 µg/L in bile, and 4.4 µg in 60 g received gastric contents (estimated total gastric contents 100 g). The cause of death was ruled to be "acute colchicine toxicity" and the manner of death "accidental."