A selective and sensitive near-infrared fluorescent probe for in vivo real time tracking of exogenous and metabolized hydrazine, a genotoxic impurity.

Abstract

Hydrazine is a well-known genotoxic impurity which may be present in some important drugs, such as isoniazid and hydralazine. It may be ingested along with the drug or generated as a metabolite in the human body. Hence, monitoring the level of hydrazine in the human body is of great importance. A hemicyanine-based NIR fluorescent probe, Hcy-DB, was designed and synthesized for hydrazine detection. This probe exhibited a dramatic off-on NIR fluorescence response toward hydrazine in PBS-DMSO buffer and the detection limit was calculated to be 4.38 ppb. The bioimaging of hydrazine in living H1975 cells was successfully demonstrated. Moreover, the real time imaging of hydrazine, either injected as a foreign agent or generated as a metabolite of isoniazid, was demonstrated in mice and the results clearly disclosed the hydrazine level variation in the liver and kidneys. The injected exogenous hydrazine was mainly distributed in the kidneys and then excreted slowly. After the intragastric administration of isoniazid, hydrazine was quickly generated as a metabolite in the liver and reached a maximum in about 20 min, and then it was excreted slowly through the kidneys. Generally, the investigation provided a promising tool to monitor the level of hydrazine in vivo and thus help to evaluate and control its toxicity more rationally.