Synthetic cannabinoids (SCs) are a series of structurally related analogs continually created to evade surveillance and sanction, which pose more severe hazards compared with traditional marijuana. Currently, synthetic cannabinoids have become the most diverse and widely abused classes of new psychoactive substances (NPS). Considering the serious threat posed by these substances, our country has regulated all categories of synthetic cannabinoids since July 1, 2021, which means that the establishment of rapid screening strategies of synthetic cannabinoids shall be further promoted. Here, a method of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 112 synthetic cannabinoids in hair. The hair samples were firstly extracted with methanol, and the supernatant was taken for injection. Then 0.1% formic acid aqueous solution and 0.1% formic acid acetonitrile solution were used as mobile phase, and the ACQUITY UPLC BEH C18 chromatographic column was used for separation. The samples were analyzed under the scheduled MRM mode through two or three ion channels specially selected for each compound with optimized collision energy. A major challenge in this experiment is the differentiation of isomers or synthetic cannabinoids with a similar mass number especially for the mass spectrometry, so the optimization of chromatographic conditions was thoroughly investigated, and a general chromatographic method for the 112 synthetic cannabinoids and two complementary methods for isomers were finally determined. The methodological validation results showed that the detection limits of 112 synthetic cannabinoids ranged from 0.5 to 5 ng/g, the linear correlation coefficient (r) was better than 0.999 0, and the matrix effect and extraction recovery were 81.0%-117.8% and 80.4%-119.7% with different concentration levels (1, 5, 25, 100 ng/g), respectively. Finally, fifteen hair samples in actual cases were detected by this method and the results showed that five kinds of synthetic cannabinoids were identified and quantified with the contents range of 1.4-48.2 ng/g. Furthermore, the results also exhibited minimal background interference in chromatograms of actual samples, indicating that this established strategy has high quantitative accuracy and can be widely used in the qualitative and quantitative analysis of practical cases. In addition, the method has high efficiency in high-throughput screening, which can simultaneously identify all kinds of synthetic cannabinoids reported in China so far. [ABSTRACT FROM AUTHOR]