Metal-organic frameworks (MOFs) are porous hybrid materials composed of metal ions and organic linkers, characterized by their crystallinity and by the highest known surface areas. MOFs structures present accessible cages, tunnels and modifiable pores, together with adequate mechanical and thermal stability. Their outstanding properties have led to their recognition as revolutionary materials in recent years. Analytical chemistry has also benefited from the potential of MOF applications. MOFs succeed as sorbent materials in extraction and microextraction procedures, as sensors, and as stationary or pseudo-stationary phases in chromatographic systems. To date, around 100 different MOFs form part of those analytical applications. This review intends to give an overview on the use of MOFs in analytical chemistry in recent years (2017–2019) within the framework of green analytical chemistry requirements, with a particular emphasis on possible toxicity issues of neat MOFs and trends to ensure green approaches in their preparation.

Four metal-organic frameworks (MOFs), specifically UiO-66, UiO-66-NH₂, UiO-66-NO₂, and MIL-53(Al), were synthesized, characterized, and used as sorbents in a dispersive micro-solid phase extraction (D-µSPE) method for the determination of nine pollutants of different nature, including drugs, phenols, polycyclic aromatic hydrocarbons, and personal care products in environmental waters. The D-µSPE method, using these MOFs as sorbents and in combination with high-performance liquid chromatography (HPLC) and diode-array detection (DAD), was optimized. The optimization study pointed out to UiO-66-NO₂ as the best MOF to use in the multi-component determination. Furthermore, the utilization of isoreticular MOFs based on UiO-66 with the same topology but different functional groups, and MIL-53(Al) to compare with, allowed us for the first time to evaluate the influence of such functionalization of the ligand with regards to the efficiency of the D-µSPE-HPLC-DAD method. Optimum conditions included: 20 mg of UiO-66-NO₂ MOF in 20 mL of the aqueous sample, 3 min of agitation by vortex and 5 min of centrifugation, followed by the use of only 500 µL of acetonitrile as desorption solvent (once the MOF containing analytes was separated), 5 min of vortex and 5 min of centrifugation. The validation of the D-µSPE-HPLC-DAD method showed limits of detection down to 1.5 ng·L⁻¹, average relative recoveries of 107% for a spiked level of 1.50 µg·L⁻¹, and inter-day precision values with relative standard deviations lower than 14%, for the group of pollutants considered.

The mixed-ligand strategy was selected as an approach to tailor a metal–organic framework (MOF) with microextraction purposes. The strategy led to the synthesis of up to twelve UiO-66-based MOFs with different amounts of functionalized terephthalate ligands (H-bdc), including nitro (-NO₂) and amino (-NH₂) groups (NO₂-bdc and NH₂-bdc, respectively). Increases of 25% in ligands were used in each case, and different pore environments were thus obtained in the resulting crystals. Characterization of MOFs includes powder X-ray diffraction, infrared spectroscopy, and elemental analysis. The obtained MOFs with different degrees and natures of functionalization were tested as sorbents in a dispersive miniaturized solid-phase extraction (D-µSPE) method in combination with high-performance liquid chromatography (HPLC) and diode array detection (DAD), to evaluate the influence of mixed functionalization of the MOF on the analytical performance of the entire microextraction method. Eight organic pollutants of different natures were studied, using a concentration level of 5 µg· L⁻¹ to mimic contaminated waters. Target pollutants included carbamazepine, 4-cumylphenol, benzophenone-3, 4-tert-octylphenol, 4-octylphenol, chrysene, indeno(1,2,3-cd)pyrene, and triclosan, as representatives of drugs, phenols, polycyclic aromatic hydrocarbons, and disinfectants. Structurally, they differ in size and some of them present polar groups able to form H-bond interactions, either as donors (-NH₂) or acceptors (-NO₂), permitting us to evaluate possible interactions between MOF pore functionalities and analytes’ groups. As a result, extraction efficiencies can reach values of up to 60%, despite employing a microextraction approach, with four main trends of behavior being observed, depending on the analyte and the MOF.

In-vial microextraction is probably the simplest microextraction technique because it eliminates centrifugation and/or filtration steps while offering short extraction and desorption times. However, it has had limited applicability, mostly involving polydimethylsiloxane coatings and gas chromatography applications. Quite recently, one study introduced metal-organic framework (MOF)-coated glass vials for environmental analyses and liquid chromatography, thus combining the advantages of MOFs as adsorbents with the advantages of the in-vial approach, while not limiting the application to volatile analyses. Besides, a much higher exposure of the MOF to the sample due to the thin film coating available within the vial's inner walls is attained. Clearly, the applicability of this format for bioanalysis has not been evaluated, as there are not many stable and reusable sorbents useful for biological samples presenting high protein content. Besides, the in-vial technique must demonstrate to be valid for low-availability samples, such as saliva. A vial with 2 mL-capacity and coated uniformly with a MOF has been developed to analyze saliva in a thin film solid-phase microextraction approach, while keeping an adequate analytical performance using only 50 μL of solvent for desorption. The procedure only requires 12.5 min of operation. Interestingly, the issues related to pore-blocking of the crystalline materials by proteins present in the saliva samples are solved with a simple cleaning protocol that also ensures a high reusability of the vials (more than 50 times). Seven bisphenols were determined in saliva with these devices, reaching limits of detection down to 0.10 μg L^-1, and with inter-vial and inter-day precision values as RSD (in %) lower than 15% at a low concentration level (2.0 μg L^-1). A device is presented to analyze complex saliva samples with a novel miniaturized MOF-coated vial ensuring proper reusability, while addressing the challenge of protein clogging and, at the same time, keeping adequate analytical performance with short analysis times. This approach represents significant progress in the bioanalytical sample preparation field, particularly when using sorbent porous materials integrated within miniaturized devices.