Selecting 2-chlorovinylarsonic acid(CVAOA) as the biomarker,a determination method of ultra-trace CVAOA in human urine specific to lewisite exposure was developed.The conditions for derivatization were optimized by orthogonal experiments,and the results were as follows:thiolation by a 1∶1 000 mole ratio of CVAOA to 3,4-dimercaptotoluene(DMT) for 5 min at room temperature.Enrichment and purification of the derivative product(CVAOA-DMT) based on the optimum headspace-solid phase microextraction(HS-SPME) conditions,and then analysis of the derivative by gas chromatography-mass spectrometry in selective ion monitoring(GC-MS-SIM).The linear calibration range was from 50.0 pg/mL to 500 ng/mL(r2=0998 5),and the relative standard deviations(RSDs) were less than 10%.The limit of detection was 7.6 pg/mL and the limit of quantitation was 23 pg/mL.The recoveries of lewisite exposed urine samples at the low,middle and high concentration levels ranged from 97.6% to 105% with the RSDs of 4.4%-7.1%.The method exhibited a satisfactory universality with its high sensitivity,precision and accuracy,and could be applied in different laboratories.