## 1 Introduction  
Since the launch of neonicotinoids (NEOs) into the market in the early 1990s to replace organophosphate, carbamate, and pyrethroid insecticides, they have become the most widely used insecticides worldwide. NEOs, including acetamiprid (ACE), clothianidin (CLO), dinotefuran (DIN), imidalcoprid (IMI), thiazolcprid (THI), thiamethoxam (THIA), and nitenpyram (NIT), are systemic insecticides. Globally, NEO use has continued to increase, with the total production valued at US$ 2.5 billion and with registrations in \(>\)120 countries [1]. NEOs are highly water soluble, and because of their systemic mode of action, they have been detected in soils, plants, surface water, pollens, honey, and food [2; 3; 4; 5]. Therefore, they may be hazardous to ecosystems and human health through different routes, including ingestion (e.g., contaminated food, water), inhalation, and dermal contact. Toxicological data from animal studies indicate possible genotoxicity, cytotoxicity, impaired immune function, and reduced growth at low levels [7]. The European Food Safety Authority (EFSA) Panel on Plant Protection Products and their Residues stated that ACE and IMI may damage the developing human nervous system [8].  
Milk is an indispensable nutritional food in the daily diet of humans. To ensure the safety of milk for consumers, governmental agencies have established maximum residue limits (MRLs) for some NEOs. For NEO residues in milk, the Codex Alimentarius Commission has set the MRL range of 20-200 \(\upmu\)g/kg [9]. To accurately determine NEO residues in milk, a fast, sensitive, and robust analytical procedure is vital. From the analytical perspective, milk is a challenging matrix because of its high content of fats, which are extracted along with analytes.  
Several methods have been proposed for determining the levels of NEO residues in food samples, including honey, fruits and vegetables, rice, tea, chicken, pork, and eggs [4, 10, 11, 12]. For solid samples, the most widely proposed pretreatment method is the so-called quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique, followed by solid-liquid extraction. For liquid samples, solid-phase extraction (SPE), liquid-liquid extraction, and dispersive liquid-liquid microextraction are common [12]. Little information is available regarding the quantitative analysis of NEO residues in milk. Some pretreatment methods have been proposed for the analysis of NEOs in milk, such as SPE with the Chem Elut cartridge [13, 14], hydrophilic-lipophilic-balanced (HLB) cartridge [10], C18 cartridge [15, 16], liquid-liquid extraction [17], ionic liquid-magnetic nanocellulose microextraction [18], and the QuEChERS method [19, 20].  
With regard to the analytical methods, NEOs quantification in milk are mainly determined by high-performance liquid chromatography (HPLC) coupled to diode-array detection (HPLC-DAD) [14], HPLC with DAD and a mass spectrometry (HPLC-DAD/MS) [18], and HPLC or ultra HPLC (UHPLC) coupled to tandem mass spectrometry [(U)HPLC-MS/MS) [10, 13, 15, 16, 17, 18, 19]. However, some methods have limitations in terms of instrument sensitivity and the number of NEOs that can be simultaneously analyzed. In order to achieve very accurate quantification and very low detection limits, the use of stable isotopically labeled standards (IS) UHPLC-MS/MS are essential.  
In this study, a method was developed for simultaneously determining the levels of seven NEOs (ACE, CLO, DIN, IMI, THI, THIA, and NIT) residues in milk, and it was validated for the analysis of commercial milk samples in Taiwan. The proposed method is fast, accurate, and sensitive, and it is a liquid-liquid extraction and IS UHPLC\(-\)MS/MS method.