Surface imprinting technology means preparing imprinted materials by controlling templates to locate at the surface or in the proximity of materials surface to create more effective recognition sites (Chen et al., 2016). It can overcome the disadvantages of low binding capacity and difficulty in elution of traditional MIPs. Core-shell structured MIPs are the major type of surface imprinting MIPs, owing to the increased surface area and larger binding capacity, and thus, they are widely used for detecting antibiotic residues (Ji et al., 2018; Liu et al., 2018; Negarian et al., 2019; Qin et al., 2019; Zhu et al., 2019a).

Nanoimprinting technology is the technique of preparing nanosized MIPs. Nanomaterials have a large surface area and more binding sites, which can effectively improve the binding capacity of MIPs. To a certain extent, the problems of fewer target sites and low mass transfer rate of large-size MIPs are solved. Moreover, the nanostructured MIPs can be directly used without grinding, simplifying the experimental operation. The commonly used methods to synthesize nano-MIPs microspheres include precipitation polymerization (Liu et al., 2018), sol-gel (Li G. et al., 2018; Diaz-Alvarez et al., 2019), and core-shell polymerization (Qin et al., 2019). Nanoimprinting technology can be divided into zero-dimensional, one-dimensional, and two-dimensional types (Li and Wang, 2020).

LCRP overcomes the disadvantage that the growth rate of the traditional radical polymerization chain is not easy to control and causes the particle size distribution of the polymer to be in a narrow range. Among them, atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization are the most commonly used ones. LCRP technology has been increasingly used for the determination of antibiotic residues (Liang Y. et al., 2018; Zhao et al., 2018; Cai et al., 2019; Li et al., 2020b; Cai et al., 2021) and other environmental contaminants (Azizi et al., 2020).

Multitemplate imprinting strategy means that two or more targeted analytes are as templates to prepare MIPs and thereby there are multiple recognition sites of template molecules in one imprinted polymer material (Wang et al., 2019). Due to the expansion of binding sites and recognition ability of MIPs, simultaneous recognition, enrichment, and separation of multiple targets can be realized, which greatly saves time and improves the utilization efficiency of MIPs. It has great potential in multiresidue and high-throughput analysis of complex samples (Wei et al., 2016; Xu et al., 2018; Lu et al., 2019; Dil et al., 2021).

The multifunctional monomer imprinting strategy is to take advantage of two or more functional monomers to interact with template molecules; by giving full play the synergistic effects of multiple functional monomers, MIPs selectivity is significantly enhanced and thereby enrichment ability. The strategy has been increasingly applied in antibiotics determination (Li G. et al., 2018; Li Z. et al., 2018; Cai et al., 2021).

Dummy template imprinting strategy is also called pseudotemplate imprinting strategy, which uses similar compounds to the target compounds as a template in the shape, size, structure, and functionality. It is a high requirement and especially suitable for the target compounds that are costly, flammable, explosive, easy to degrade, and having too low solubility. The strategy can effectively avoid template leakage pollution or inaccurate results. The most common method is the computer-aided design of dummy template toward MIPs (Song et al., 2017). MISPE prepared by dummy template imprinting strategy is widely used in the detection of antibiotic residues (Song et al., 2019; Zhang Z. et al., 2020; Gao et al., 2021).

SAs residues are closely related to food and environmental safety levels. The pollution sources of SAs antibiotics mainly include medical sources (patients feces and urine, antibiotics remaining on medical supplies, losses in the production of antibiotics by pharmaceutical enterprises, etc.), animal sources (animal excrement and urine, leakage of sewage from farms, etc.), and aquaculture (overuse of antibiotics in the process of farming, etc.) (Zhang Y. et al., 2020). The key to detection is to develop fast, efficient, and highly selective pretreatment methods. Common SPE materials for SAs include HLB, C18, and Oasis MCX which are relatively general and commercially available, but they lack selectivity for SAs. MISPE can identify, extract, and enrich the target substances with high selectivity and specificity and has high adsorption capacity and stability. At the same time, various SPE devices have become smaller and are easier to operate. MISPE has been widely used coupled with chromatographic determination toward SAs in complex samples (Wang J. et al., 2018; Fonte et al., 2018; Huang et al., 2018; Kechagia et al., 2018; Xu et al., 2018; Zhao et al., 2018; Zhu et al., 2019a; Zhu et al., 2019c; Gao et al., 2021; Zhao et al., 2021).

In order to improve the selective adsorption performance of MIPs in strong polar solvents, Zhu et al. (2019a) synthesized sulfamethoxazole (SMZ) imprinted polymers in methanol by using a new ionic liquid (IL) functional monomer, namely, 1-butyl-3-vinylbromidazole (BVIM-Br). The MIPs exhibited highly specific recognition properties toward the three commonly found SAs (SMZ, sulfamonomethoxine (SMM), and sulfadiazine (SDZ)) in methanol, while low adsorption ability was displayed for the interferents. Then, a MISPE methodology was developed and successfully applied to effective enrichment of trace SMZ in soil and sediment samples, followed by HPLC analysis. The limits of detection (LODs) were all as low as 5 μg/L. The present research can offer an important reference for influential MIPs preparation in aqueous media. Furthermore, Zhu et al. (2019c) prepared SMM surface imprinted polymers in the strong polar solvent of methanol with 1-allyl-3-vinylimidazolium chloride (AVIM-Cl) IL as a functional monomer. The developed MISPE coupled with HPLC was established for the selective extraction and sensitive determination of trace SMM in soil and sediment samples. The recoveries were high to 95.0–105.0% and the LOD was low to 1.0 μg/L. Such MIPs materials have a broad application prospect in the pretreatment of various complex samples.

Zhao et al. (2021) synthesized hydrophilic magnetic MIPs (HMMIPs) on the surface of silanated Fe₃O₄ via surface imprinting technique and using SDZ as a template molecule and employed them as DSPE adsorbents for the enrichment and purification of 10 SAs prior to HPLC-UV detection in chicken, cow milk, and goat milk samples. Under the optimal experimental conditions, good linearity in the range of 5 μg/L to 10 mg/L was exhibited, low LODs ranged from 0.57 to 1.50 μg/L, and high spiked recoveries were between 85.09 and 110.93%. The HMMIPs-DSPE method can provide a potentially applicable way for the sensitive, reliable, simple, and rapid detection of various drug residues. In the previous work (Zhao et al., 2018), water-compatible MIPs were also prepared by combining RAFT with reflux precipitation polymerization (RPP), and the resulting MISPE coupled with HPLC-MS/MS succeeded in the enrichment and determination of six SAs in animal-derived foods and water samples.

Gao et al. (2021) fabricated magnetic carbon nanotube dummy MIP (MCNTMIP) nanocomposite by surface imprinting technique and used it as MSPE adsorbent to realize the simultaneous separation and enrichment of 13 SAs (SDZ, sulfathiazole (ST), sulfamerazine (SM1), sulfamethazine (SM2), sulfamethizole (SMZO), SMM, sulfachloropyridazine (SCP), sulfadoxine (SO), SMZ, sulfisoxazole (SFZ), and sulfaquinoxaline (SOX), sulfadimethoxine (SDM), and avermectin B1a) in fish and shrimp samples. Figure 3 illustrates the process of MIPs preparation and MSPE application. The MCNTMIP displayed a simple magnetic separation, specific molecular recognition, and high adsorption capacity. Coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) determination of all the SAs, the LODs were all as low as 0.1 μg/kg, and the recoveries were in a range of 90.2–99.9%. Moreover, the precision values ranged from 0.5 to 9.1%. Consequently, the developed MCNTMIP-MSPE method can be routinely utilized for the trace analysis of SAs to ensure food quality and consumer safety.

QNs are a class of antibacterial drugs with 1,4-dihydro-4-oxyquinoline-3-carboxylic acid structure. They are widely used in clinical diagnosis and treatment, animal disease prevention, and growth promotion because of their advantages such as wide antibacterial spectrum, good efficacy, small toxic and side effects, simple synthesis, and low cost. The residual concentration of QNs is low, mostly ng/L or ng/kg. Excessive or improper use of QNs in animal-derived food has potential carcinogenic, teratogenic, and mutagenic effects, thus threatening human health. Almost all countries have formulated the maximum residual limit standard (MRLS) for quinolone antibiotics. MISPE is widely used in the determination of QNs in complex substrates (Li G. et al., 2018; Wang J. et al., 2018; Hu et al., 2018; Rodriguez-Gomez et al., 2018; Barahona et al., 2019; Zhu et al., 2019b; Ma and Row, 2019; Li et al., 2020b; Tian et al., 2020; Yu et al., 2020; Cai et al., 2021; Soares et al., 2021).

Our group (Lu et al., 2019) prepared novel double-template MIPs (dt-MIPs) via a simple and facile precipitation polymerization method with norfloxacin (NOR) and enrofloxacin (ENR) as templates and used them in DSPE combined with HPLC-DAD for the simultaneous selective enrichment and determination of two fluoroquinolones (FQs) in environmental water samples. Figure 4 schematically shows the dt-MIPs preparation and DSPE process. The well-prepared dt-MIPs exhibited good adsorption capacity and selectivity for NOR and ENR, with high enrichment factors of 71 and 61, respectively. Good linearity was obtained in the range of 1–200 µg/L. The LOD and limit of quantification (LOQ) values for NOR were 0.22 and 0.67 µg/L, respectively, and 0.36 and 0.98 µg/L for ENR. Satisfactory recoveries of the two FQs were attained of 80.9–101.0% with relative standard deviations (RSDs) of 0.9–6.9% from spiked lake, sea, and tap water samples. This study not only offered a good method choice for FQs detection but also enriched the research connotation of multitemplate imprinting.

Yu et al. (2020) developed a MISPE method for the simultaneous enrichment of 11 FQs [ofloxacin (OFX), gatifloxacin (GAT), NOR, ciprofloxacin (CIP), difloxacin, pefloxacin (PEF), sarafloxacin (SAR), enoxacin (ENX), floxacin, ENR, and lomefloxacin (LOM)] in water by UPLC/MS-MS determination. The attained LODs of FQs were within 6–150 ng/L. The recoveries of all the targeted FQs in sample matrices were higher than 75%, and RSDs were below 15%. The developed MISPE-UPLC/MS-MS proved to be effective for the determination of FQs in wastewater and sludge samples.

Li et al. (2020b) successfully prepared restricted-access media-imprinted nanomaterials (RAM-MIPs) on the surface of the metal-organic framework (MOF) by RAFT. Figure 5 shows the synthesized route of the RAM-MIPs. Then, they were applied for the DSPE of five FQs (OFX, PEF, NOR, ENR, and GAT) in milk and river water samples prior to HPLC-UV detection. The method attained low LODs, namely, 1.02–3.15 μg/L for milk samples and 0.93–2.87 μg/L for river water samples, respectively, as well as satisfactory recoveries, namely, 80.7–103.5% and 85.1–105.9%, respectively. In comparison with other materials, the RAM-MIP materials are significantly advantageous owing to their simple preparation conditions, uniform and controllable imprinting layer thickness, fast adsorption rate, and so on. The present study demonstrates that RAM-MIP (prepared with MOF as a matrix)-based SPE has broad prospects toward efficient extraction of trace FQs in complex samples.

Cai et al. (2021), using surface-initiated ATRP and sarafloxacin (SAR) as a template, constructed monodisperse RAM-MIPs, and three methods were adopted, as illustrated in Figure 6. The optimum synthesis method was to combine 4-vinylpyridine (VP) and methacrylic acid (MAA) (1:3) as monomers and to select an 8:1:32:8 ratio of a template molecule, cross-linker, and restricted-access functional monomer. The RAM-MIPs showed a high IF (6.05) and the selectivity coefficients were 1.86–2.64 between SAR and other FQs. The RAM-MIP-packed SPE showed higher enrichment ability toward SAR in a complex protein-containing solution than that of traditional MIP-packed one. As a result, the MISPE coupled with the HPLC-UV method achieved a low LOQ for SAR at 4.23 ng/g and the high mean recoveries within 94.0–101.3%. The present study indicated a great application potential of the RAM-MIPs based SPE for trace analysis in complex samples. Furthermore, the proposed functional monomer ratio and rebinding method opened a new way for devising and synthesizing various MIPs.

de Oliveira et al. (2016) used ENRO as the template molecule to synthesize MIP1, adopted a multitemplate imprinting strategy (four studied FQs as the template molecules) to synthesize MIP2, and utilized it for the simultaneous PT-SPE of the four FQs (CIP, ENR, marbofloxacin (MARBO), and NOR) in human urine samples. By comparison, MIP1 proved a better adsorbent, and high extraction efficiency was obtained to ENRO (96.0%). Figure 7 schematically shows the apparatus employed for PT-MIP-μ-SPE. It was possible to extract CIPRO (∼40%), NOR (∼40%), and MARBO (∼80%) due to the similarity of the molecular structures. The method attained good linearity from 39 to 1,260 ng/ml for individual FQ, and the LOQ for individual FQ was as low as 39 ng/ml. Finally, the validated PT-MIP-μ-SPE method was proved to be practically applicable, through the preliminary cumulative urinary excretion study after administrating CIPRO to a healthy volunteer.

TCs, as a kind of broad-spectrum antibiotics produced by Streptomyces, have caused serious harm to the ecological environment and human health because of their wide use and hence residues. Huang L. et al. (2019) used TC, chlortetracycline (CTC), and doxycycline (DC) as the templates and magnetic graphene oxide (Fe₃O₄/GO) as the supporting material to prepare magnetic multi-MIPs. Then chip-based magnetic multi-MIPs monolithic capillary array columns were constructed for simultaneous MSPE and determination of the TCs in eggs samples. High affinity and specificity to TC, CTC, and DC were shown and the IFs reached 86–104-fold. The LOD values ranged from 3.0 to 5.5 μg/kg. Therefore, the MISPE columns afforded hopeful perspectives for the facile extraction of antibiotics from complicated samples.

Aguilar et al. (2020) synthesized the MIPs by precipitation polymerization using TC as template molecule and applied them for dispersive SPME (DSPME) and removal of TC residues in milk samples. The molecular recognition properties and selectivity of MIPs against four TCs (TC, oxytetracycline (OT), CTC and DC) were evaluated, and then high selectivity was demonstrated for the four TCs. The MIP-based DSPME process provided a high removal ratio between 81.83 and 96.44% with RSD<5% in all cases. Compared to classical removal methods, the present method was faster and required lower solvent consumption and minimum sample manipulation. Therefore, a promising prospect can be expected for facilely synthesizing efficient and selective adsorbents and utilizing MISPE for the simultaneous removal of multiple contaminants residues.

Ma et al. (2020) prepared magnetic molecularly imprinted biochar microspheres with specific adsorption of TCs (TC; OT) by Pickering emulsion polymerization. The obtained materials were employed as adsorbents for extraction and purification of TCs in actual samples (fish, chicken, and tap water). This method was simple in preparation process and cost-effective; the synthesized polymer was a regular spherical structure with magnetic response characteristics, which can simplify the extraction and purification of sample pretreatment. It offers a new idea for the application of MIPs based biochar in contaminant detection in food samples.

CAP is a kind of broad-spectrum antibiotics isolated from Streptomyces venezuelae. Because its long-term and high dose use easily caused granulocytosis, aplastic anemia, and other diseases, China has banned its use in feed-animals (especially laying hens and dairy cows) and required CAPs residues to be mandatory test items in all aquatic products, livestock, and poultry products (Zhang et al., 2021). BLAs are a broad class of antibiotics, and their residues mainly come from agricultural and veterinary drugs, medical drugs, and wastewater treatment discharges from sewage plants. They pose potential threats to the human body and ecology. For example, a few patients will have allergic reactions to BLAs, and the residual antibiotics in the soil will affect the growth of plant roots and seed germination, etc. In addition, the pollution of Antibiotic-Resistant Bacteria (ARB) and Antibiotics Resistance Gene (ARG) caused by the abuse of BLAs and other antibiotics is threatening human health and ecological safety (Li et al., 2020a). MALs are widely used in clinical and veterinary medicine fields, with a broad spectrum of antimicrobial effects, especially for animal husbandry and aquaculture (Liang and Zhang, 2021). At present, more and more efforts have been devoted to the monitoring of MALs residues.

Using MISPE technology with excellent performance, the trace detection of various antibiotics in diverse complex substrates has been realized (Li Z. et al., 2018; Lian and Wang, 2018; Xie et al., 2018; Negarian et al., 2019; Qin et al., 2019; Garza Montelongo et al., 2020; Tan et al., 2020). For example, Qin et al. (2019) developed a straightforward method for selective separation of CAP from marine sediment samples. CAP-MMIPs were synthesized via surface imprinting and nanoimprinting technologies. The material has a perfect core-shell structure, excellent thermal stability, and high selectivity toward CAP. The CAP-MMIPs were employed for fast and selective SPE of CAP followed by HPLC-DAD. An excellent linearity was attained from 0.1 to 20 mg/L (R² = 0.999, n = 3), and the LOD was 0.1 μg/L. The spiked recoveries were between 77.9 and 102.5% with low RSDs (< 6.3%). Good reusability was achieved (at least 5 times) by the regeneration and there was hardly any loss of selectivity and adsorption capability. Such MMIPs-SPE method can provide a vital alternate to traditional extraction ones for preparing environmental samples.

Teixeira et al. (2018) prepared 1-vinylimidazole-co-trimethylolpropane trimethacrylate- (1-VI-co-TRIM-) based MIPs adsorbent for PT-SPE of abamectin (ABA), eprinomectin (EPR), and moxidectin (MOX), coupled to HPLC-UV determination. The performance criteria for linearity, sensitivity, precision, accuracy, recovery, robustness, and stability were systematically assessed and were within the recommended guidelines. The validated PT-MIP-SPE proved to be economical, simple, easy-to-perform, and potentially applicable for the extraction of MALs in complicated samples.

Nascimento et al. (2020) firstly synthesized a new selective adsorbent based on magnetic molecularly imprinted polypyrrole-conducting polymer (MMIPPy) and applied it to the MSPE of praziquantel (PZQ) enantiomers [(R)-(−)-PZQ and (S)-(+)-PZQ] combined with HPLC-DAD determination. Under optimal conditions, excellent linearity was attained in a range of 0.01–10 µg/ml, with correlation coefficients higher than 0.98 and RSDs less than 15%. The LOQ was 0.01 µg/ml for both enantiomers, and RSDs and relative errors were below 20%. The method was applied satisfactorily for the determination of PZQ enantiomers from sheep milk samples with the possibility to other analytes in different complex matrices. The economical, simple, and easy-to-perform MMIPPy-MSPE method suggested great application potential for antibiotics residues determination.