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Determination of carbamazepine in urine and water samples using amino-functionalized metal–organic framework as sorbent
© The Author(s) 2018
- Received: 5 October 2017
- Accepted: 26 June 2018
- Published: 30 June 2018
A stable and porous amino-functionalized zirconium-based metal organic framework (Zr-MOF-NH2) containing missing linker defects was prepared and fully characterized by FTIR, scanning electron microscopy, powder X-ray diffraction, and BET surface area measurement. The Zr-MOF-NH2 was then applied as an adsorbent in pipette-tip solid phase extraction (PT-SPE) of carbamazepine. Important parameters affecting extraction efficiency such as pH, sample volume, type and volume of eluent, amount of adsorbent, and number of aspirating/dispensing cycles for sample solution and eluent solvent were investigated and optimized. The best extraction efficiency was obtained when pH of 100 µL of sample solution was adjusted to 7.5 and 5 mg of the sorbent was used. Eluent solvent was 10 µL methanol. Linear dynamic range was found to be between 0.1 and 50 µg L−1 and limit of detection for 10 measurement of blank solution was 0.05 µg L−1. This extraction method was coupled to HPLC and was successfully employed for the determination of carbamazepine in urine and water samples. The strategy combined the advantages of fast and easy operation of PT-SPE with robustness and large adsorption capacity of Zr-MOF-NH2.
- Pipette-tip solid phase extraction
- Zirconium-based metal–organic framework
- Urine analysis
Carbamazepine (CBZ, 5H-dibenzo [b,f] azepine-5-carboxamide) often used as anticonvulsant drug for treatment of epilepsy [1, 2]. Whenever a patient consumes CBZ, about 2–3% of this drug will excrete unchanged through his urine and enters into environmental aquatic ecosystems . Studies confirmed that CBZ can be present in wastewater (up to 6.3 µg L−1) [4–7], surface water (up to 1.1 µg L−1) [8, 9], and drinking water (around 30 ng L−1) [10, 11]. Biodegradation of CBZ is very difficult in environmental media owing to its low solubility and stability in water. Therefore, several methods including advanced oxidation processes (AOPs), adsorption on various sorbent media have been employed for the removal and extraction of it [1, 2, 12–14].
In recent years, some sample preparation techniques such as liquid–liquid extraction (LLE) , dispersive liquid–liquid microextraction (DLLME)  and solid-phase extraction (SPE)  have been used for isolation and extraction of CBZ in complicated matrices. SPE is a prevalent procedure for pre-treatment of various pharmaceutical analytes due to its reproducibility, high recovery and simple operation. Miniaturized SPE has been developed to overcome on the problems raised by conventional SPE processes such as matrix effect, low detection limit, losses of analytes, and environmental problems due to consumption of large amounts of organic solvents.
Pipette-tip solid-phase extraction (PT-SPE) is a convenience, and microscale of SPE method which reduces amount of sorbent and reagents and saves the analysis time [18–20]. This technique required several repeated aspirating/dispensing cycles to complete the extraction procedure.
Intrigued by the above-mentioned findings, we encouraged to prepare and use the bio inspired sponge, amino-functionalized Zr-MOF, for micro-scale solid phase extraction and determination of the carbamazepine. Several parameters affecting extraction efficiency including pH, type and volume of eluent, volume of sample solution, and amount of sorbent, number of draw/eject of sample solution and eluent solvent type were tested and optimized. Finally, the method was used for the determination of carbamazepine in urine and water samples.
Chemicals and materials
All reagents (analytical grade) were purchased from Sharloa (Spain) and used as received, except HPLC solvents which were of chromatographic grade. All aqueous solutions were prepared using ultra-pure Milli-Q® purification system. 20 µL pipette-tips (Dragon Lab, China) were used as micro columns. Carbamazepine was obtained from Sigma-Aldrich (St. Louis, MO, USA).
Synthesis of Zr-MOF-NH2 sorbent
Zr-MOF-NH2 was synthesized according to the Hupp/Farha method  with minor modifications. In a 25 mL vial, dimethyl formamide (5 mL) and concentrated HCl (2.85 mL, 850 mmol) were added to 0.125 g, (0.54 mmol) of ZrCl4 before being sonicated for 10 min. A mixture of 2-aminoterephthalic acid (0.134 g, 0.75 mmol) and dimethyl formamide (10 mL) were then added to the clear solution and the mixture was sonicated for 20 more minutes. Afterwards, the capped vial was placed in a pre-heated oven at 80 °C for 15 h. After cooling to room temperature, the solid Zr-MOF-NH2 was filtered and washed with dimethyl formamide, and then with ethanol several times. In order to evaporate any solvents, this product was left for several hours under the hood and then was dried under reduced pressure (80 °C, 3 h). The solid Zr-MOF-NH2 was then activated at 120 °C for 12 h under high vacuum prior to measuring N2 isotherms.
Characterization of Zr-MOF-NH2
Fourier-transform infrared spectroscopy (FT-IR) spectra were recorded using a Perkin-Elmer FTIR (USA). Powder X-ray diffraction (PXRD) patterns were recorded on a Philips X’pert diffractometer (Germany) with monochromated Cu Kα radiation (λ = 1.5418 Å) within the range of 1.5° < 2θ < 38°. Samples for scanning electron microscopy (SEM) were sputtered with a layer of Os (5-nm thickness) prior to taking images on a Hitachi S-4800 SEM (Japan) with a 15.0 kV accelerating voltage. BET surface area measurements were made at 77 K with liquid nitrogen on a Micrometrics TriStar 3020 (N2) surface area analyzer (Britain). Zr-MOF-NH2was degassed for 12 h at 120 °C before the measurement under a stream of nitrogen.
Determination of CBZ was performed on an HPLC manufactured by Cecil company (England), equipped with a C18 ACE column (250 × 4.6 mm, 5 μm particle sizes) and a UV detector at wavelength of 210 nm. A mixture of water: acetonitrile (75:25) were used as mobile phase (isocratic elusion). Column was thermostated at room temperature. Injection volume and flow rate were 10 µL and 1 mL min−1, respectively.
CBZ Extraction procedure
5 mg of Zr-MOF-NH2 was transferred to a 20 µL pipette-tip as micro column and attached to 100 µL variables sampler (Isolable, Germany). 100 µL sample solution was then introduced to column and passed over the sorbent and dispensed back to a 1 mL test-tube. The same sample solution was loaded into the micro column for 5 cycles. Adsorbed CBZ was then eluted by 10 µL of methanol in a 1 mL test-tube for 7 cycles, from which, 20 µL was injected to HPLC. Urine sample was collected from a healthy female and stored at − 80 °C and used throughout all experiments. This participant was not using supplements containing CBZ. Before start of the experiments, sample was brought to the room temperature, of which 250 µL was transferred to a canonical centrifuge tube. After addition of 1 mL of 1 M ammonium persulphate, it was heated in a water bath for 60 min at 95 °C. Then, this solution was brought to room temperature and was extracted by means of the suggested procedure. Tap water was obtained from laboratory and sample was filtered through a 0.45 µm Whatman filter paper and spiked with carbamazepine.
Characterization of adsorbent
The morphology of the MOF was examined by scanning electron microscopy (SEM) (Fig. 4). Unlike the octahedral crystal shape of Zr-MOF-NH2 obtained by other methods , the SEM images of the nominal MOF showed aggregates of quasi-spherical particles between 100 and 200 nm.
Optimization of PT-SPE procedure
To achieve the best extraction efficiency, we tried to optimize the conditions influencing the extraction processes as described below. All optimization experiments were performed with 10 µg L−1 of CBZ solution.
Effect of pH
Amount of adsorbent
Effect of volume of sample solution
Effect of volume of eluent
Effect of draw/eject of sample solution and eluent
The procedure of aspiration of a solution into pipette tip and dispensed back into the same sample tube is called aspirating/dispensing (or draw/eject) cycles, which a critical factor for PT-SPE extraction. Therefore, the influence of this parameter on the extraction efficiency was examined between 3 and 20 cycles. After 5 cycles, the extraction of CBZ from sample solution was found to be complete. Meanwhile, the best elusion of CBZ from the sorbent was occured at 7 cycles of draw/eject of eluent. In higher number of cycles, the efficiency was decreased, which is probably due to the back extraction of the analyte from adsorbent into the sample solution, causing a decrease in the recovery.
Reusability of the sorbent
To investigate the stability and reusability of the Zr-MOF-NH2 packed micro column, after desorption of CBZ from the adsorbent, the column was washed five cycles with methanol and then five cycles with deionized water. After that, several extraction and elution operation cycles were carried out under the optimized conditions. The result of experiments indicated that the adsorbent could be reused at least for eight times with a decrease of only 5% in extraction recovery. As the powder PXRD patterns of the Zr-MOF-NH2 before and after adsorption shown in the Fig. 3, the crystallinity of the MOF was reserved during the experimental conditions, confirming the stability of the MOF under the experimental conditions.
The adsorption capacity of the Zr-MOF-NH2 was determined by the batch experiments. For this purpose, a standard solution containing 2000 mg L−1 of CBZ was applied. The amount of adsorbed CBZ was calculated by determination of difference between initial and final concentration of CBZ after adsorption. The maximum sorption capacity was defined as the total amount of adsorbed CBZ per gram of the Zr-MOF-NH2. The obtained capacity was found to be 32 mg g−1. High adsorption capacity indicated that large porosity and large surface area of adsorbent.
Analytical figures of merit for Zr-MOF-NH2 for extraction of CBZ
Linear Dynamic range (μg L−1)
R2 (determination coefficient)
Repeatability (RSD%) (50 μg L−1)
Limit of detection (µg L−1)
Total extraction time (min)
Determination of carbamazepine in real samples
Evaluation of carbamazepine in real samples
Concentration found (µg L−1)
Spiked at concentration (µg L−1)
Comparison of proposed method with other methods
Comparisons of the proposed methods with other methods for extraction of CBZ
LOD (µg L−1)
LOQ (µg L−1)
Molecularly imprinted polymer
SPE/graphene- silica gel
SPE/modified sulfur nanoparticles
SPE/oasis HLB cartridges
A porous amino-functionalized metal organic framework containing missing-linker defects was firstly prepared and then applied for pipette-tip solid phase extraction of a drug, carbamazepine. The total time of analysis, including extraction was less than 12 min. The Zr-MOF-NH2 sorbent was used for at least eight extractions without any significant change in its capacity or repeatability. Only 5 mg of the sorbent was enough for filling the PT. The presence of more open active zirconium sites, more numbers of hydroxyl groups, the large porosity, very high surface area, the amino functionality, and the suitable pore size of the Zr-MOF-NH2 could improve the extraction of CBZ. Moreover, the fast, inexpensive, effective, reliable, applicable and organic solvent-free method can open up new practical applications for MOFs in SPE based analytical techniques.
MRRK did the practical work and wrote the manuscript. Both ARO and BRK co-wrote the manuscript and ARO also synthesized MOF. MK co-wrote the manuscript and planned the study. All authors read and approved the final manuscript.
Authors hereby thanks from health laboratory of Zabol University of Medical Sciences for cooperation to perform experiments.
The authors have declared no competing interests.
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