High-Throughput Liquid Chromatography- Vacuum Differential Mobility Spectrometry-Mass Spectrometry for the Analysis of Isomeric Drugs of Abuse in Human Urine

Abstract

The use of differential mobility spectrometry at low pressure coupled to liquid chromatography-mass spectrometry (LC-vDMS-MS) was investigated for the analysis of thirteen drugs of abuse (DoA) including: cocaine, ecgonine methyl ester, cocaethylene, benzoylecgonine, norcocaine, tramadol, isomeric pairs of metabolites; O-desmethyl-cis-tramadol and N-desmethyl-cis-tramadol, and cannabinoids; Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabidiol, 11-hydroxy-Δ9-tetrahydrocannabinol, 11-nor-9carboxy-Δ9-tetrahydrocannabinol, 11-nor-9carboxy-Δ9-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 5 cannabinoids including the isomers THC/CBD and three THC metabolites. 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 intra- and inter-day 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.