Ketamine is one of the most frequently abused illicit drug in China while hydroxylimine and o-chlorophenyl cyclopentyl ketone are the main chemical precursors.Most of articles on drug profiling were about tracing the geographical origins or determining synthesizing routine of “worldwide popular drugs” such as heroin,cocaine,methamphetamine and MDMA,by analyzing impurities or by-products of the samples,few articles were about ketamine and its chemical precursors.In this article,ketamine and its chemical precursors profiling were investigated by determine the relevant impurities.Unlike methamphetamine having more than one chemical precursor(ephedrine and phenylactone) and many synthesizing methods(Emde,Ngai,Birch and Reductive amination),all ketamine samples in illicit factory were produced by heating hydroxylimine to reconstruct its molecular structure,and all hydroxylimine samples were synthesized with o-chlorophenyl cyclopentyl ketone which were synthesized by Grignard reagent reaction or Friedel-Crafts reaction.Therefore,it is very important to determine the impurities of samples from the o-chlorophenyl cyclopentyl ketone synthesizing reaction.Gas chromatography-mass spectrometry(GC-MS) was used to detect the impurities in the seized o-chlorophenyl cyclopentyl ketone samples,2-chlorobenzonitile and byproducts of Grignard reagent reactions,including cyclopentanone,cyclopentanol,cyclopentylcyclopentane,2-cyclopentylcyclopentanone and 2-cyclopentylcyclopentanol were signed as the profiling impurities.By synthesizing o chlorophenyl cyclopentyl ketone in lab and detecting it by GC-MS,these 6 profiling impurities were proved to be produced by the reaction of 2-chlorobenzonitile and grignard reagents.Coupling reactions and oxidation reactions of Grignard reagent to produce these profiling impurities were discussed.Hydroxylimine samples were extracted by liquid liquid extraction method,and 4 of those profiling impurities were detected in hydroxylimine samples by GC-MS while the samples were purified in the recrystallization step.Ketamine samples were detected by head space injector GC-MS(HS/GC-MS),and 2 of those profiling impurities were detected while the samples were purified by proceeding recrystallization.Finally,all hydroxylimine and o-chlorophenyl cyclopentyl ketone samples,and 102 of 105 ketamine samples were found to contain 2 of the profiling impurities at least.It could be inferred that Grignard reagent method is the most common routine for the synthesization of o-chlorophenyl cyclopentyl ketone in illicit factory.