**1. Introduction**

The addition of drugs (abuse or illegal use) to animal food to promote growth and protect animals can represent a potential risk of contamination of food matrices. Drugs, such as antibiotics, estrogens, non-steroidal anti-inflammatory drugs (NSAIDs), and β-agonists, which are usually used in feedstuffs, can contaminate different food products, mainly meat, milk, and dairy products, causing health problems and also serious diseases [1]. In particular, the abuse of antibiotics in food-producing animals, which contributes to the increase in risk of the transfer of antibiotic resistance from animals to humans, is a very important issue for human health. For this reason, the European Union (EU) and the Food and Drug Administration (FDA) established restrictive regulations for the control of pharmacologically active substance residues and fixed maximum residue limits (MRLs) in edible animal tissues to preserve foodstuff of animal origin and consumers [2–4].

The need of sensitive and rapid analytical techniques to detect and quantify pharmacologically active compounds, unauthorized drugs included, in animal food and foodstuff of animal origin has become mandatory for food security. Therefore, over the years, the necessity to develop and validate new analytical methods has increased [5]. The Commission Decision 2002/657/EC reported the technical guidelines and performance criteria for method validation for the control of the different residues [6]. In addition, there is a lack of regulation for veterinary drug residues (for example, for fluoroquinolones used as antimicrobials) in many foods, including baby foods [7].

EU guidelines suggest the use of the liquid chromatography (LC) technique; in particular, LC coupled with mass spectrometry (MS) was the most used approach to detect and analyze drug residues in complex matrices, such as milk and dietary products [8–12]. In addition, ion mobility spectrometry (IMS) coupled with MS represented a very promising powerful tool to detect analytes in traces [13].

Capillary electrophoresis (CE) with its well-known advantages, such as high efficiency, low consumption of sample and buffer, and rapidity, represents a potential alternative to LC methods in the analysis of drugs in different fields, including food analysis [14–16]. Another important advantage of CE rests in the versatility of applications thanks to the development of different CE separation modes. The simple addition of different molecules (surfactants, chiral selectors, polymers, particular electrolytes, and organic modifiers) to the buffer or the modification of the capillary inner wall with new packaging materials gave origin to different separation mechanisms and selectivity, increasing CE versatility and potential applications [16–19].

In particular, the use of electrospray ionization (ESI), matrix-assisted desorption/ionization (MALDI), and inductively coupled plasma (ICP) as CE-MS interfaces improved food analysis by increasing CE sensitivity [20,21]. In fact, CE-MS represents the ideal technique to detect analytes in traces with important implications in food contaminants and residue analysis [15,16].

In addition, advances in electrochemical detectors, such as CE-contactless coupled detection (CE-CCD) and CE-capacitively coupled contactless conductivity detection (CE-C4D), offered very sensitive methods [22,23]. Furthermore, the development of miniaturized CE systems (microchip-CE devices) allowed the monitoring of food analytes with rapidity and sensitivity, and their use was particularly important in the detection of frauds or contaminations [24–26].

Due to the complexity of food matrices, which are mainly rich in lipids, carbohydrates, and proteins, a pre-concentration step was necessary to detect drug residues in trace amounts. This became mandatory because of the intrinsic poor sensitivity of CE [27]. Solid phase extraction (SPE) and miniaturized SPE are the most used procedures, not only for the pre-concentration step, but also for the sample clean-up. New SPE sorbents with high adsorption capacity and high resistance were studied, giving origin to selective materials for some drugs and also generating advanced high-throughput procedures able to extract different drug classes [28,29]. In addition, advances in on-chip SPE-CE procedures also allowed low-abundance analytes with high sensitivity to be analyzed [30]. Recently, the combination of traditional liquid-liquid extraction (LLE) and SPE procedures or advanced liquid extraction techniques, such as dispersive liquid-liquid microextraction (DLLME), was successfully applied to detect analytes in trace, increasing CE sensitivity [31–33].

Finally, the development of on-line procedures in which pre-concentration techniques were integrated with the CE instrumentation had many advantages, such as minimal sample loss, low cost, and rapidity [34].

In this review, we focused the attention on the potential of CE in veterinary drug residue analysis, considering the versatility of different CE-modes (mainly capillary zone electrophoresis, CZE; capillary electrochromatography, CEC; micellar electrokinetic chromatography, MEKC; nonaqueous capillary electrophoresis, NACE). CE methods and advanced sample preparation procedures combined with CE techniques in the last decade were also discussed. The main CE-modes were summarized, subdividing drugs into antibiotics (classified according to different molecular structures) and other drugs (estrogens, non-steroidal anti-inflammatory drugs, NSAIDs, and β-agonists).
