Silica Supported Metal Organic Framework Composites As Adsorbent For Solid-phase Extraction Of Benzodiazepines In Urine Sample

Objectives For the monitoring of benzodiazepines?BZPs?in biological samples,solid-phase extraction?SPE?is a required step to remove the interfering compounds and preconcentrate the analytes from the sample matrix.The sorbent as the key of SPE technique,influences on the sensitivity and accuracy of the BZPs analytical method.Metal-organic frameworks 808?MOF-808?was used to extract the BZPs owing to large surface area,high porosity and the exceptional chemical resistance in organic solvents.However,considering the diameter of MOF-808?100-500 nm?,there is difficulty in direct packing it into classical SPE cartridge and avoiding any leakage during the SPE process.Additionally,it is difficult to isolate the adsorbents from the sample solution completely in dispersive SPE,leading to low extraction accuracy and poor precision.To overcome these obstacles,a novel silica supported metal organic framework 808 core-shell adsorbent?MOF-808@SiO₂?was fabricated via the controllable in-situ growth of MOF-808 shell on the surface of SiO₂ particles.The composites were applied as an effective adsorbent and coupled with high performance liquid chromatography for the determination of three BZPs in urine samples.Methods 1 MOF-808@SiO₂ was synthesized using carboxylate-terminated SiO2?SiO₂-COOH?particles as nucleation,Zr?IV?as central ion and 1,3,5-benzenetricarboxylic acid as ligand by solvothermal reaction.The cycle of carboxylation of SiO₂?1,2,and 3?and the concentration of Zr⁴⁺(0.005,0.01 and 0.02 mmol.mL^-1)were investigated.MOF-808@SiO2 was characterized by scanning electron microscopy?SEM?,X-ray powder diffractometry?XRD?and nitrogen adsorption experiment.2 The prepared MOF-808@SiO₂ was developed as adsorbent for the SPE of three BZPs from urine samples.Parameters such as NaCl concentrations(0,25,50,75 and 100 mmol.L^-1),pH of the sample solution?4.0,4.6,5.2,5.8,6.4,7.0 and 7.6?,loading volumes?4,6,8 and 10 mL?,eluting solutions?acetone,methanol,methanol/NH₄OH?98/2,v/v?and acetonitrile?and eluting volumes?1,2 and 3 mL?were optimized.3 The analytical figures of merit were validated including linear range,limit of detection,limit of quantification,accuracy and precision of the method.In addition,the adsorptive performance of MOF-808@SiO₂ was compared with commercial adsorbents including C₁₈,hydrophilic-lipophilic balance?HLB?and weak cation exchange?WCX?.Results 1 The cycle of carboxylation of SiO₂ was fixed at 3 and the concentration of Zr⁴⁺was selected as 0.02 mmol.mL^-1for the fabrication of MOF-808@SiO₂.SEM images revealed the successful fabrication of MOF-808 crystals on the SiO₂-COOH and the uniform structure of the prepared composites.The characteristic signal of MOF-808 and the typical peaks of SiO₂-COOH were observed on the XRD pattern of MOF-808@SiO₂.This provided another proof that the MOF-808 nanocrystal shell was successfully formed on the surface of SiO₂-COOH.In addition,the surface area of MOF-808@SiO₂ was found to be 314.5 m².g^-1.These properties made MOF-808@SiO₂ powerful as a SPE adsorbent.2 The MOF-808@SiO₂ based SPE coupled with high performance liquid chromatography was applied for the monitoring of BZPs in urine samples.The extraction of BZPs was achieved by using 300 mg of MOF-808@SiO₂ with no adjustment of ionic strength and pH of the sample solution,and the sample volume of 8 mL and 1 mL of acetonitrile were adopted for further study.3 Under the optimized conditions,the present method gave the linear range of 1.5-200 ng.mL^-1with correlation coefficient?r?of 0.999.The limits of detection?S/N = 3?and the limits of quantification?S/N = 10?ranged from 0.4 to 0.6 ng.mL^-1and 1.5 to 2.0 ng.mL^-1,respectively.The enrichment factor of 16.2-19.2 was achieved and the recoveries for spiked urine samples with three levels(10,20 and 40 ng.mL^-1)were in the range of 81.2%-95.9%.The intra-day and the inter-day precisions were 3.4%-7.1% and 3.2%-9.1%,respectively.Besides,MOF-808@SiO₂ showed superior or comparable performance in comparison with conventional adsorbents including C₁₈,HLB and WCX.Conclusions A novel MOF-808@SiO₂ adsorbent was fabricated via in-situ growth approach and coupled with high performance liquid chromatography-diode array detector for the analysis of BZPs in urine samples.The in-situ growth approach overcame the shortcomings in direct packing or dispersion of MOF-808 in solution,facilitating its application in SPE.The surface area of SiO₂-COOH was found to be 228.5 m².g^-1and the as-prepared MOF-808@SiO₂ showed increased surface area to be 314.5 m².g^-1.The adsorption efficiency of the analytes on SiO₂-COOH reached 35.1%-43.7%,while MOF-808@SiO₂ provided the greatly enhanced adsorption efficiency of 100%.No adjustment of ionic strength and pH of the solution allowed robust and convenient manipulation.Moreover,the enrichment factor of three BZPs was in the range of 16.2-19.2.The proposed method was successfully applied for the accurate and effective determination of BZPs in urine samples.Figure 20;Table 7;Reference 121...