Detection of ketamine and its metabolites in human hair using an integrated nanoflow liquid chromatography column and electrospray emitter fritted with a single porous 10 μm bead

Targeting metabolites incorporated into hair following drug administration is useful for evidential purposes as this approach can aid in differentiating between administration and passive exposure. Greater analytical sensitivity is required than for targeting the parent drug alone. A 20 μm i.d. fused silica capillary column with an integrated electrospray emitter fritted with a single porous 10 μm polymeric bead has been successfully fabricated to facilitate this purpose. The sensitivity gains through the use of these integrated single fritted columns coupled to a nanoelectrospray source (nanoflow–LC nanoESI) over conventional liquid chromatography–tandem mass spectrometry (LC–MS/MS) columns was explored by their application to the detection of ketamine and its phase I metabolites in human hair. Hair was collected from 4 volunteers following the administration of a small oral dose of ketamine (50 mg) and subsequently analysed by the capillary–LC nanoESI approach. The drug and its metabolites were extracted from hair using solid phase extraction following a methanolic wash, pulverisation with a ball mill and acid digestion. From a 50 μL extract, 1 μL was injected and the method provided a limit of detection estimated to be 5 fg on column for ketamine and norketamine and 10 fg for dehydronorketamine. The single porous frit minimises extra column band broadening and offers an alternative fritting approach which reduces the blocking of the electrospray emitter, in comparison with other approaches such as sintering and polymerisation.

► A 20 μm i.d. capillary column with was fritted with a single 10 μm porous bead. ► The column consisted of an integrated electrospray emitter. ► Dehydronorketamine was detected in hair samples for the first time.