Table 2.

Summary of studies applying metabolomics for biomarker search of acute drug intake or manipulation.

Parent compound	Changed endogenous metabolites	Experimental setup	Sample preparation	Analytical conditions	Data evaluation	Reference
MA	5-oxoproline Saccharic acid Uracil 3-hydroxybutyrate Adipic acid Glucose Glucose-6-phosphate Fructose 1,6-bisphosphate TCA cycle intermediates	Untargeted Rat plasma and urine MA vs. control n = 6 per group	LLE Derivatization CH3-O-NH2 MSTFA	GC-HRMS CP-SIL 8 (30 m × 0.25 mm i.d., 0.25-um) He TOF CE-MS/MS FunCap-CE type S 50 mM NH4Ac (pH9) QTrap	MetAlign SIMCA-P +	Shima et al., 2011
GHB	glycolate succinate creatinine	Untargeted Human urine Controlled administration Before/after design n = 12 per group	Lyophilization	NMR Bruker AVANCE II 600 14.1 T 1D 1H NMR 2D 1H-1H COSY 2D 1H-1H TOCSY 2D 1H- 13C HSQC 2D 1H-13C HMBC	SIMCA 14 Metaboanalyst	Palomino-Schatzlein et al., 2017
GHB	b-citryl glutamic acid	Untargeted Human urine Random GHB and reference samples n = 3 GHB n = 100 reference		LC-HRMS Eclipse XDB C18 (150 × 4.6 mm, 5 um) H2O, 0.1% FA ACN, 0.1% FA ESI pos/neg-qTOF	Agilent Profinder Agilent Mass Profiler Professional R version 2.11.1	Piper et al., 2017
GHB	Glycolate Succinylcarnitine	Untargeted Human urine Placebo vs. GHB controlled, crossover n = 19 each Authentic samples n = 10 GHB n = 20 control	Dilution/filtration	LC-HRMS XSelect HSST RP-C18 (150 mm × 2.1 mm, 2.5 μm) 10 mM NH4COOH, 0.1% FA MeOH, 0.1% FA Merck SeQuant ZIC HILIC (150 mm × 2.1 mm, 3.5 μm) 25 mM NH4Ac, 0.1% HOAc ACN, 0.1% HOAc ESI pos/neg—qTOF Fullscan Additional run in MS/MS mode (DDA)	Progensis Qi Metaboanalyst 4.0	Steuer et al., 2018c
Synthetic cannabinoids/ herbal blends	Scopoletin N,N-bis (2-hydroxyethyl) dodecylamine	Untargeted Human saliva Tobacco vs. 6 different herbal mixtures n = 3 per group	PP	LC-HRMS CORTECS® C18 (100 × 2.1 mm, 2.7-μm) H2O, 0.01% FA MeOH, 0.01% FA ESI pos/qTOF	MassLynx XCMS in R EZinfo 2.0	Bijlsma et al., 2018