A liquid chromatography-tandem mass spectrometric(LC-MS/MS) method with QuEChERS and solid phase extraction(SPE) cleanup was developed for determination of 27 novel fentanyl analogs and metabolites in solid and liquid drugs.The confirmation was achieved with electrospray ionization(ESI) in positive ion mode under multiple reaction monitoring(MRM) mode,and quantified by the external standard method.The standard curves for 27 target compounds were linear in the range of 0.5-50.0 μg/L,with their correlation coefficients(r2) more than 0.99.The limits of quantitation(LOQ) were 10.0 μg/kg for solid drugs and 10.0 μg/L for liquid drugs,respectively.Recoveries at three spiked levels ranged from 84.8% to 109% with relative standard deviations(RSD) of 0.86%-8.5%.With the advantages of rapidness,simplicity,time saving,high sensitivity and good stability,the method could be applied in the qualitative and quantitative detection of fentanyl analogs and metabolites in drugs.