In forensic toxicology the identification and quantification of drugs of abuse and their metabolites in biological samples, is crucial to confirm drug intake. Drugs of abuse (e.g., cocaine, tramadol, cannabinoids, morphine, amphetamines) are illicit drugs that threaten health and social stability. The global number of drug users is expected to grow 25 % by 2050, directly impacting road safety and public health with a concomitant increase in the requirement for testing. Many analytical procedures have been described to quantified commonly encountered drugs of abuse and their metabolites, in biological matrices including saliva 2 , sweat , hair , urine and blood by liquid chromatography and gas chromatography coupled to mass spectrometry (LC-MS, GC-MS) . Ion mobility (IMS) has drawn attention for the analysis of drugs of abuse, especially for isomeric metabolites, either as a standalone system or coupled to mass spectrometry (IMS -MS). Drift time ion mobility-time of flight (DTIMS-TOF) derived collision cross section (CCS) have been used for the improved analysis of DoA in blood samples , DTIMS has been applied for fast opioid profiling in human urine using flowinjection analysis (FIA) . Gwak et al. described a drift time ion mobility -time of flight ( DTIMS)-TOFMS method for screening of 35 new psychoactive substances (NPS) in seized drug samples. Tose et al. described a travelling wave ion mobility mass spectrometry (TWIM-MS) method for isomeric separation of cannabinoids in hashish samples, marijuana and parts of the Cannabis sativa L. plant (flower and leaf). Differential ion mobility (DMS) or High Field Asymmetric Waveform Ion Mobility (FAIMS) exploits the ion mobility that occurs in the electric field in the region between two electrodes when an asymmetric waveform is applied orthogonal to the gas stream. DMS is generally combined with triple quadrupole linear ion trap, quadrupole time of flight or orbitrap and offers the possibility to add chemical modifiers (e.g., isopropanol, acetone, toluene) to the transport gas flow to tune separation selectivity, and/or improve S/N ratio. Porta et al. described a modifier-assisted differential ion mobility spectrometry-mass spectrometry (DMS-MS) hyphenated to liquid extraction surface (LESA) method for the analysis of 30 drugs of abuse and metabolites in human post-mortem kidney and muscle tissues. Mashmoushi et al. reported the separation of isomeric cannabinoids including THC and CDB by DMS-MS negative ion mode using isopropanol as modifier. A sensitive DMS-MS/MS method was developed and validated for simultaneous identification of 33 drugs and metabolites in human urine samples provided better analytical performance than immunoassay. Furthermore, DMS has been implemented to compensate for liquid chromatography selectivity loss in trap-elute approaches and open port probe sampling interface for high-throughput analysis. Gómez-Ríos et al. reported a fast quantitation of opioids isomers in human plasma using biocompatible solid-phase micro extraction (bio-SPME) and an open-port probe sampling interface . Sosnowski et al. describe the application of an in-house 3D-printed open port probe (3DP-OPP) with DMS-MS for the quantitative analysis of cocaine and tramadol isomeric metabolites in urine samples and for the screening of illicit ecstasy pills using acetonitrile as modifier. While most DMS applications have been established on systems running at atmospheric pressure, a prototype DMS working at low pressure range 4.7-30 Torr was recently developed, employing a planar-gap stage within the MS instrument envelope rising normalized electric field up to 543 Td . The effect of LC mobile phase, composition and flow rate in vDMS separation was reported Girard et al., and found to be important parameters in the optimization of vDMS performance. Being beneficial to improve the assay selectivity, and reduce analysis time, vDMS-MS was applied to the quantitative analysis of antidepressants in plasma and pyrrolizidine alkaloids in tea samples .