High-throughput liquid chromatography-vacuum differential mobility spectrometry-mass spectrometry for the analysis of isomeric drugs of abuse in human urine.

The use of differential mobility spectrometry at low pressure coupled to liquid chromatography-mass spectrometry (LC-vDMS-MS) was investigated for the analysis of 13 drugs of abuse (DoA) including the following: cocaine, ecgonine methyl ester, cocaethylene, benzoylecgonine, norcocaine, tramadol, isomeric pairs of metabolites; O-desmethyl-cis-tramadol and N-desmethyl-cis-tramadol, and cannabinoids: Δ 9 -tetrahydrocannabinol, Δ 9 -tetrahydrocannabidiol, 11-hydroxy-Δ 9 -tetrahydrocannabinol, 11-nor-9carboxy-Δ 9 -tetrahydrocannabinol, and 11-nor-9carboxy-Δ 9 -tetrahydrocannabinol glucuronide. Different parameters were optimized for isomeric separation, such as LC mobile phase composition (20%-100% methanol acetonitrile and isopropanol, flow rate: 8-100 μL/min) and DMS separation voltage. Methanol and acetonitrile significantly affected the compensation voltage of the analytes and improved DMS separation. A short trap/elute LC-vDMS-SIM/MS screening method of 1 min was developed to quantify 11 drugs of abuse (except THC/CBD), in addition to a 4-min LC-vDMS-SIM/MS method to identify and quantify five cannabinoids including the isomers THC/CBD and three THC metabolites. THC is the principal psychoactive constituent of cannabis and is a controlled substance in comparison to its isomeric counterpart CBD; this highlights the importance and challenges to resolve these isomeric pairs by analytical techniques. The signal responses were linear over a concentration range of 0.005-10 μg/mL for the DoA and 1-1000 ng/mL for cannabinoids. The intraday and interday precision were better than 12.2% and accuracy better than 115%. Urine samples from subjects who tested positive for THC and/or cocaine during roadside drug testing were evaluated to assess the performance of the methods LC-vDMS-SIM/MS and LC-MRM/MS. Results show that the developed LC-vDMS-SIM/MS method presents similar performance to LC-MRM/MS with improved sample throughput.