Purpose.- Synthetic cannabinoids (SCs) are the largest group of new psychoactive substances (NPS) monitored worldwide. We validate a rapid and sensitive liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay for the determination of 16 SCs in human hair samples. This method was successfully applied to document chronic use of JWH-122 in a 42 years-old male included in large-scale cross-sectional study in Paris. Method.- The SCs JWH-018, JWH-018-5-N(OH-pentyl), JWH-073, JWH-073-4-N(OH-butyl), JWH-122, JWH-200, JWH-019, JWH-250, AM-2201, EAM-2201, BB-22, ADB-PINACA, AKB48-5F, AB-FUBINACA, 5F-AB-PINACA, 5F-PB-22 were extracted from 20 mg of decontaminated, washed and grinded hair by a mixture of hexane/ethyl acetate (1/1, v/v) in alkaline condition in the presence of JWH-018-D11 internal standard. SCs were then separated by a gradient of formate buffer 2 mM in 0.1% formic acid (A) and acetonitrile (B) on Hypersyl Gold PFP column (100 x 2.1 mm i.d., particle size 1.9 mu m, ThermoFisher) at 30 degrees C. The detection was performed on TSQ Vantage triple-quadrupole mass spectrometer (Thermofisher, Les Ulis, France) in positive ionization and multi-reaction monitoring (MRM) modes. A lock of hair (6 cm) was sampled from a patient hospitalized for JWH 122 overdose and segmented into 3 segments: A: 0-2 cm (proximal), B: 2-4 cm and C: 4-6 cm. It was then analyzed with the present method in order to determine past use of synthetic cannabinoids. Results.- The method exhibits a good linearity (r(2) > 0.996) over the range 1-25 to 1000 pg/mg, Limits of detection and quantification ranged from 0.3 to 8 pg/mg and from 1 to 25 pg/mg, respectively (CVs <= 15%). No interference from endogenous substances with the detection of SCs and their IS was observed and the carryover was insignificant. Intraday and inter-day trueness (bias) and precision (CVs) were <= 8.2%, <= 14.3%, <= 8.3% and <= 14.9%, respectively. Overall recoveries ranged between 61 and 94% and corrected matrix effect from 31 to 110%. JWH-122 hair concentrations found in patient's hair were: (A/B/C: 200/450/430 pg/mg) in agreement with the concentrations found in the literature suggesting chronic use of JWH-122 over the last six months. Conclusion.- The present LC-MS/MS method proved to be suitable for the detection and quantification of 16 synthetic cannabinoids in human hair. (C) 2019 Societe Francaise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.