Fatal road traffic crashes are often related to multifarious risk factors, among which driving under the influence of drugs (DUID) has been reported as a significantly contributing cause. The first worry about the side-effect of influencing driving drugs is central nervous system adverse reaction, and anti-hypersensitivity drugs are a class of drugs with such side effects meanwhile has been widely used for common allergic diseases thus posing a great challenge to road safety and demanding a rapid and efficient method to detect. In this work, a method based on magnetic graphene oxide dispersive solid phase extraction (MGO-D-SPE) combined with ion mobility spectrometry (IMS) was firstly introduced for simultaneous determination of ephedrine, pseudoephedrine, diphenhydramine, promethazine and terfenadine in saliva and urine matrices. The prepared MGO was characterized by Fourier transform infrared (FT-IR) spectroscopy and thermo gravimetric analysis (TGA). Various parameters affecting extraction efficiency as well as instrumental acquisition sensitivity were studied and optimized. Under the optimum experimental conditions, the method was fully validated and the results demonstrated that the proposed method exhibited some advantages, including a good linearity covering large concentration ranges of 51.0-3040 ng ml(-1) for five anti-hypersensitivity drugs, and good accuracy was also obtained with high precision (CV% < 5.0 %). LODs and LOQs were 10.2-50.4 ng mL(-1) and 30.6-101.3 ng mL(-1), respectively. Consequently, the MGO-D-SPE-IMS methodology succeeded in building a hitherto unexplored tool for quantifying anti-hypersensitivity drugs in saliva and urine matrices of interest in DUID research field. (C) 2020 Elsevier B.V. All rights reserved.