**4. Conclusions**

In summary, ENR-*d3* was firstly synthesized as a new isotope surrogate to establish an accurate and fast quantitative method for measuring ENR residues in aquatic products with dual isotope surrogates (ENR-*d5* and ENR-*d3*) using HPLC–MS/MS. The new method can be used to perform the determination of ENR with a wide linear range from 2 to 13,122 μg/kg in a single sample preparation with excellent sensitivity, accuracy, and precision. Moreover, a high residue level of ENR, which generally leads to the overflow of the instrument response, can be directly diluted and re-calibrated by the corresponding curve with a high addition level of the other internal surrogate without repeating sample preparation. Furthermore, it was also possible to reduce the deviation of the detected value caused by the vast concentration difference between the isotope standard and target analytes. The new method was applied for the determination of ENR in positive samples for various aquatic species showing the ENR values ranging from 99.1 to 4340 μg/kg. The new method was demonstrated to be time-efficient and easy to operate, providing a practical, accurate, and precise way to determine veterinary drug residues. It is especially suitable for batch samples with a wide range of residue variations and possible high residue content.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/foods12010224/s1.

**Author Contributions:** Conceptualization, C.K. and G.Y.; methodology, C.K. and S.W.; validation, Y.T., W.S. and E.K.F.; formal analysis, Y.T. and G.Y.; investigation, Y.T. and G.Y.; resources, C.K.; writing—original draft preparation, Y.T.; writing—review and editing, C.K., W.Z. and E.K.F.; visualization, S.W. and L.X.; project administration, C.K.; funding acquisition, C.K. and G.Y.; All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the National Natural Science Foundation of China (31701698) and the Central Public-Interest Scientific Institution Basal Research Fund, ECSFR, CAFS (2018T02).

**Data Availability Statement:** The data presented in this study are available on request from the corresponding author.

**Acknowledgments:** This work was supported by the National Natural Science Foundation of China (31701698) and the Central Public-Interest Scientific Institution Basal Research Fund, ECSFR, CAFS (2018T02).

**Conflicts of Interest:** The authors declare no conflict of interest.
