Diatomite-Supported Zeolitic Imidazolate Framework-8composites As Adsorbent For Solid-Phase Extraction Of Benzodiazepines In Urine Sample

Objectives Benzodiazepines（BZDs）are a kind of commonly used psychoactive drugs and their long-term use may produce the risk of dependence and cognitive disturbance.Besides clinical therapeutic usage,BZDs are also illegal abused by criminals in narcotic,robbery,rape and other related cases.When analyzing the level of BZDs,solid-phase extraction process is required to enrich analytes and remove impurities before instrument analysis,which determines the time and cost of the entire analysis method.In current study,a novel diatomite supported zeolitic imidazolate framework-8 sorbent（ZIF-8@Dt-COOH）was in-situ fabricated and developed for solid-phase extraction of three BZDs（triazolam,midazolam and diazepam）in urine followed by high performance liquid chromatography-diode array detection.Methods 1 ZIF-8@Dt-COOH was easily prepared by in-situ growth method using Zn²⁺as central ion,2-methylimidazole as the organic ligand and carboxylate-terminated Dt（Dt-COOH）particles as nucleation.Two parameters of Zn²⁺concentration(0.04,0.08 and 0.12mmol.m L^-1)and carboxylation cycle of Dt（1 and 2）were optimized.The prepared ZIF-8@Dt-COOH was characterized by Fourier transform infrared spectra,X-ray powder diffractometry and scanning electron microscopy.2 ZIF-8@Dt-COOH was applied as sorbent for isolation of BZDs in urine samples.Main extraction parameters were optimized in detail,including ionic strength(0,5,10 and 15 mmol.L^-1 Na Cl),p H of solution（3.8,4.4,5.0,5.6,5.8,6.4,7.0 and 7.6）,loading volume（6,8,10 and 12 m L）,washing solution（NH4OAc,Na H2PO4,H2O and ACN/H2O）,elution solvent（ACN,acetone and Me OH）and elution volume（2,3,4 and 5 m L）.3 Under the optimal experimental conditions,the validation of the method was performed and a comparison with the commercial sorbents（PLS,CX and C18）was carried out to validate the adsorption performance of ZIF-8@Dt-COOH（2×）under the same conditions.Results 1 The concentration of Zn²⁺was fixed at 0.08 mmol.m L^-1 and the cycle of carboxylation of Dt was selected to be 2 to construct ZIF-8@Dt-COOH sorbent.Fourier transform infrared spectra and X-ray powder diffractometry results revealed the successful synthesis of ZIF-8 on Dt-COOH（2×）surface.Scanning electron microscopy images showed that regular dodecahedron ZIF-8 nanocrystals with an average particle diameter of 300-400nm were clearly observed on Dt-COOH（2×）.2 The optimal conditions were shown as follows:ZIF-8@Dt-COOH（2×）amount,150 mg;ionic strength and p H of the solution,no influence;sample volume,8 m L;washing,Na H2PO4(25 mmol.L^-1,p H=5);elution,4 m L of Me OH.3 The proposed method gave linearity of three BZDs in 2-500 ng.m L^-1（r≥0.9995）.Limits of detection（S/N=3）and limits of quantification（S/N=10）were 0.3-0.4 ng.m L^-1 and1.0-1.3 ng.m L^-1,respectively.In addition,the average recoveries spiked at 5,10 and 20ng.m L^-1 changed from 80.0%to 98.7%,with the intra-day and inter-day precisions of 1.4%-5.2%and 1.5%-8.2%,respectively.Besides,the proposed method provided effective purification performance and gave the enrichment factors of 24.0-29.6.Furthermore,ZIF-8@Dt-COOH（2×）exhibited superior extraction performance in comparison with commercial PLS,CX and C18 sorbents.Conclusions In current study,a novel ZIF-8@Dt-COOH（2×）sorbent was in-situ fabricated and developed for solid-phase extraction of three BZDs in urine followed by high performance liquid chromatography-diode array detection.ZIF-8@Dt-COOH（2×）was performed by mechanical stirring in 70℃water bath for 20 min,offering a convenient and fast synthesis.Compared with the bare Dt-COOH（2×）,the extraction efficiency for BZDs was significantly improved from 20.1%-39.0%to 100.0%,and the developed method provided effective purification performance and gave the enrichment factors of 24.0-29.6.The proposed method was successfully employed for the accurate and convenient determination of BZDs in biological samples.Figure 18;Table 10;Reference 148...