RATIONALE: Significant advances have been made in the preparation of different morphologies of magnesium oxide (MgO), but the relationship between MgO morphology and its interactions with therapeutic drugs is rarely studied. Herein, we investigated the interactions between different morphologies of MgO and therapeutic drugs using paper spray mass spectrometry. METHODS: Different morphologies of MgO including trapezoidal, needle-like, flower-like and nest-like structures were prepared through a facile precipitation method. The as-obtained MgO particles were then coated onto the surface of filter paper via vacuum filtration strategy. The coated papers with different morphologies of MgO were used as the substrates for paper spray mass spectrometry to explore the interactions between different MgO and therapeutic drugs. RESULTS: Through investigating the interactions between different morphologies of MgO coated papers and therapeutic drugs, it demonstrated that, in contrast to the trapezoidal, needle-like and nest-like MgO coated papers, different drugs in dried blood spots (DBS) were more favourably eluted off from the paper coated with flower-like MgO due to its weaker surface basicity. Also, the signal intensities of different drugs during paper spray were highly dependent on their elution behaviours. CONCLUSIONS: Paper spray mass spectrometry (MS) provides an avenue to elaborate the surface properties of MgO with different structures. The surface basicity of MgO played a crucial role in determining the elution behaviours of therapeutic drugs in DBS, and a more favourable elution behaviour tended to result in a higher MS signal. Copyright © 2016 John Wiley & Sons, Ltd.Magnesium oxide (MgO), as an exceptionally important inorganic material, has found wide application in many fields including catalysts, [1][2][3][4][5][6] adsorption and separation, [7][8][9] chemical sensing, [10,11] electrical [12] and optical [13] devices, toxic waste remediation, [14] and superconductor products, [15] due to its unique surface basic property as well as nontoxic and environmentally friendly nature. Over the past decades, many protocols such as the sol-gel route, [16] the precipitation method, [9,17,18] the hydrothermal method, [19] chemical vapour deposition, [20] precursor decomposition, [21] and so on [22,23] have been developed to fabricate meso-, micro-and nanostructured MgO. The reported morphologies of MgO are mainly composed of spherical structure, [9] parallelogram, [18] nanowires, nanotubes or nanobelt, [24] nanoflower, [25] nanosheets, [26] cubes, [27] whiskers, [28] stacks of plates, [29] rectangular parallelepiped, [30] columnar structure, [31] and corraline. [32] In recent years, numerous studies have demonstrated that the change in the morphology of MgO can alter its surface properties, [1,2,[33][34][35] which was formerly considered constant. [21] For example, many reports have evidenced that the catalytic performance of MgO was closely related with its shape, illustrating an apparent morphologydependent phenomenon...