Rapid analysis of Lewisite metabolites in urine by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry.

A high-throughput method has been developed for determining Lewisite [dichloro(2-chlorovinyl)arsine] exposure by measuring the urine metabolite 2-chlorovinylarsonous acid (CVAA) and the oxidized metabolite 2-chlorovinylarsonic acid (CVAOA). The rapid sample preparation included a simple dilution of 400 microL of urine with 40 microL of water and 1 mL of buffer containing an internal standard and brief centrifugation prior to analysis by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (ICP-MS). CVAOA and CVAA were eluted isocratically with retention factors of approximately 3.0 and 4.2, respectively, from a reversed-phase polar embedded column with a cycle time of 5 min per sample. The dynamic reaction cell, typically used to remove polyatomic isobaric interferences, was not required for ICP-MS analysis because of the resolution of chloride from arsenical peaks of interest. This method was used to detect CVAA and CVAOA in the urine of a rat administered Lewisite up to 24 h after exposure. The method demonstrated linearity over at least three orders of magnitude and had a method detection limit of 1.3 microg/L as CVAA (1.4 microg/L CVAOA). The relative standard deviations for quality control samples ranged from 3 to 6%. The method was sensitive and selective with no false positives in 100 different urine samples collected from individuals with no known exposure to Lewisite. Ninety-six samples could be analyzed in an 8-h day.