**1. Introduction**

Dopamine (DA) and uric acid (UA) often coexist in the biological fluids, such as blood serum, urine, and extracellular fluids, which play a vitally significant role on the regulation of human physiological functions and metabolic activities [1]. As an essential catecholamine neurotransmitter, DA plays a pivotal role in regulating the functions of cardiovascular and central nervous systems, adjusting emotions, and maintaining hormonal balances [2]. The dysfunction of DA possibly causes many neurological disorders like Parkinson's syndrome, Alzheimer's diseases, and schizophrenia [3–5]. For a heathy individual, the DA levels in biological matrixes generally vary from 0.01 μM to 1 μM. The response signals of DA are often susceptible to interferences from endogenous biomolecules i.e., ascorbic acid (AA) and UA. Therefore, it remains a grea<sup>t</sup> challenge for the fast and precise detection of DA. As another critical biomolecule in human body, UA is commonly regarded as the metabolic product of purine [6]. Generally, the UA level is 4.1 ± 8.8 mg/100 mL for a healthy individual [7]. The abnormal concentration of UA in physiological fluids likely leads to several disorders including pneumonia, hyperuricemia, and gou<sup>t</sup> [8]. Thus, the levels of DA and UA in physiological fluids have become important indicators or biomarkers for healthcare and clinical diagnosis. Therefore, it is extremely necessary to propose some e fficient and reliable approaches toward the simultaneous determination of DA and UA.

Up until now, various detection approaches have been reported for detecting DA and UA, such as chemiluminescent [9], HPLC [10,11], fluorometry [12], spectrophotometry [13], and surface plasmon resonance [14]. These techniques are very reliable, but they often involve cumbersome and time-consuming procedures that require large instruments, experienced technicians, and even a large amount of poisonous solvents [15]. Recently, electrochemical approaches have drawn growing attention for the determination of bioactive compounds, food dyes, and pollutants, owing to their considerable advantages such as being inexpensive, facial operation, high e fficiency, good selectivity, and sensitivity [16–20]. In addition, DA and UA are highly electroactive biomolecules, which are more suitable for electrochemical detection. However, bare electrodes often su ffer from electrode fouling and cross-interference issues, which result in poor sensitivity and reproducibility [7,21]. To address the issues, various nanomaterials were developed to construct electrochemical sensors.

As a versatile transition metal oxide, MnO2 has been intensively utilized in energy storage, catalysis, and sensors because of its peculiar properties including low-cost, more abundance, high-catalytic activity, and environmental friendliness. Until now, a variety of nanostructured MnO2 such as nanowires [16,22], nanorods [17,23,24], nanotubes [25,26], microspheres [27,28], and nanoflowers [29,30] have been prepared, characterized, and even used in electrochemical determination. Among these morphologies, MnO2 nanoflowers (MnO2NFs) have drawn considerable attention, attributing to their pore structure and large specific surface area. As sensing materials, MnO2 nanoflowers have been used for the detection of lead ion [29], ractopamine [30], salbutamol [30], guaiacol [31], vanillin [31], hydrogen peroxide [32], and DA [33]. These studies demonstrate that MnO2 nanoflowers improve the electrochemical performances significantly. But their poor dispersibility and electrical conductivity have impeded widespread applications in electrochemical sensors.

To resolve this problem, an effective strategy is to composite nanostructured MnO2 with graphene materials, which not only effectively improve the dispersibility, but also endow a synergistic effect towards sensing target analytes. However, the electrical conductivity of graphene cannot be fully controlled due to the lack of bandgap [34]. In this regard, many approaches have been proposed to modify the electron transfer and surface chemical properties, among which the doping of nitrogen into graphene has displayed enormous potential for widespread applications [35]. Compared to pristine graphene, N-doped reduced graphene oxide (NrGO) possesses a more biocompatible C-N microenvironment, a much larger functional surface area, a better electrical conductivity, a higher ratio of surface-active groups to volume, and enhanced electrocatalytic effects [35,36]. Therefore, NrGO has been widely used to construct a variety of electrochemical sensors. For example, Yang and coworkers [37] reported a facie one-step hydrothermal preparation of Fe2O3/NrGO nanohybrids toward DA detection. Fe2O3/NrGO showed superior electrocatalytic activity toward DA oxidation, with a broad detection range (0.5 μM–0.34 mM), a low limit of detection (LOD, 0.49 μM), and good sensitivity (418.6 μA mM−<sup>1</sup> cm<sup>−</sup>2). Chen et al. [38] prepared NrGO/MnO nanocomposite via the freeze-drying technique to construct a selective electrochemical sensor for the detection of DA in the coexistence of UA and AA. Although NrGO has been intensively utilized in electrochemical sensing, as far as we know there is no report available for the use of MnO2/N-doped graphene composite for the simultaneous detection of DA and UA.

Herein, MnO2NFs/NrGO nanocomposites were prepared by a facile, cost-effective and highly efficient route rather than the conventional hydrothermal method. Specifically, MnO2NFs were prepared by a slow addition of MnSO4 into KMnO4 solution followed by a simple stirring procedure, then composited with NrGO nanosheets with an ultrasonication assistant. The combined virtues of MnO2NFs and NrGO nanosheets are expected to enhance electrochemical sensing properties, which has been proven by using the MnO2NFs/NrGO as an efficient electrocatalyst for the simultaneous determination of DA and UA in serum samples. The proposed sensor showed remarkable catalytic capacity toward the oxidation of DA and UA, with two detection ranges (0.2–6.00 μM and 6–100 μM), low LOD (36 and 29 nM for DA and UA respectively), and good selectivity as well as reproducibility.

#### **2. Materials and Methods**
