Analysis of 2,4‐Dinitrophenol in Postmortem Blood and Urine by Gas Chromatography–Mass Spectrometry: Method Development and Validation and Report of Three Fatalities in the United States

Abstract

2,4-dinitrophenol (2,4-DNP) is a compound used in the early 1900s as a weight-loss drug but later prohibited due to its severe adverse effects, including death. It has however been attracting interest, due to its weight-loss properties, and appears to be re-emerging in forensic casework. As 2,4-DNP is available for use in industry and as a pesticide and easily accessible online, the dissemination of this drug can be fast. The compound exerts its effects through inhibition of ATP synthesis, and corresponding thermogenic energy loss which can be fatal. A method for qualitative and quantitative analysis of 2,4-DNP in blood and urine specimens using GC-MS with hydrogen as carrier gas is described. The method was validated and displayed acceptable performance parameters with linearity (R 2 higher than 0.998), inter-assay imprecision (lower than 10.6%), intra-assay imprecision (lower than 10.7%), and extraction efficiency (92.1%). Stability of 2,4-DNP in blood and urine was studied, and the drug was stable up to 30 days refrigeration or frozen. Six cases in United States suspected to be related to 2,4-DNP were analyzed. Three cases were found to be positive for 2,4-DNP. Concentrations of 2,4-DNP were in the range of 61.6-220 mg/L in urine and <3-114 mg/L in blood. Based on our findings, we suggest that medical examiners and forensic toxicologists be aware of the reappearance of 2,4-DNP, including this compound as a target in death investigations related to weight-loss drugs.

2,4-dinitrophenol enhances cisplatin and etoposide cytotoxic activity on prostate cancer cell line

“…The concentration of 2,4-DNP at 100 µM was within the IC 20-40 range for the studied cell lines; hence, this concentration was chosen for future research. The chosen concentration was lower than the concentration range determined in the biological fluids of patients demonstrating symptoms of poisoning [8][9][10]30]. To evaluate the effects of the decoupling of oxidative phosphorylation to the cytotoxicity of cisplatin and etoposide, the prostate cancer cells were incubated simultaneously with both the uncoupler (2,4-DNP) and mentioned compounds for 48 h (Fig.…”