The Preparation Of Highly Efficient And Selective Stir Bar Coatings And Their Application In Pharmaceutical Analysis

A variety of pharmaceuticals have been used in our daily lives for the prevention, diagnosis and treatment of diseases. With the rapid development and extensive use of pharmaceuticals, the contamination, abuse and side effect of drugs have attracted increasing public attentions and pharmaceutical analysis is of great significance for drug-quality monitoring and reasonable administration. In pharmaceutical analysis for real samples, suitable sample pretreatment techniques are commonly and highly demanded. Stir bar sorptive extraction (SBSE) has been successfully applied for pharmaceutical analysis due to good reproducibility, high adsorption capacity, high recoveries, and solvent-free nature. However, only polydimethylsiloxane (PDMS), polyacrylate (PA) and ethylene glycol (EG)-silicon are commercially available coatings for stir bar at present, limiting their application towards pharmaceuticals with different polarity. Therefore, the need to develop novel stir bar coatings with high efficiency and selectivity towards pharmaceuticals with different polarity is of great urgency.The aim of this dissertation is to explore polar stir bar coatings for the efficient and selective extraction of polar and less polar pharmaceuticals, improve the water incompatiblity and low adsorptive capacity of molecularly imprinted polymer (MIP) based stir bar coatings, develop suitable coating carriers for improved extraction efficiency and extended lifetime of coated stir bar, and to establish SBSE-high performance liquid chromatography (HPLC) methods for the pharmaceutical analysis in environmental, food and biological samples. The major contents of this dissertation are describes as follows:(1) An ionic liquids (IL)-bonded sol-gel stir bar coating was prepared for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) followed by SBSE-HPLC-ultraviolet detection (UV). By using y-(methacryloxypropyl)trimethoxysilane (KH-570) as a bridging agent, 1-allylimidazolium tetrafluoroborate ([AIMHBF4]) was chemically bonded onto the bare stir bar, and the prepared IL-bonded sol-gel stir bar coating showed higher extraction efficiency (51.6-56.3%) and better adsorption/desorption kinetics (30 min) for target NSAIDs over PDMS based stir bar coating. The prepared IL-bonded sol-gel coating presented good mechanical strength and durability (chemical/thermal stability). The analytical performance of the developed SBSE-HPLC-UV method was evaluated under the optimized conditions. The limits of detection (LODs) of the proposed method for three NSAIDs were in the range of 0.23-0.31 ?g/L, and the enrichment factors (EFs) were in the range of 51.6-56.3 (theoretical EF was 100). The proposed method was successfully applied for the determination of NSAIDs in environmental water, urine, and milk samples.(2) Graphene oxide (GO) is an ideal adsorbent for polar and less polar compounds due to its hexagonal carbon network structure with oxygen-containing groups, while its strong hydrophilicity and water solubility limited its application in sample pretreatment techniques. Herein, GO was composited with polyethyleneglycol (PEG) or polyaniline (PANi) through intermolecular interactions to improve its stability, and the GO/PEG and GO/PANi composite coated stir bars were prepared by sol-gel technique. Compared with GO/PANi composite and PDMS coated stir bar, the prepared GO/PEG composite coated stir bar exhibited higher extraction efficiency for five fluoroquinolones (FQs). Besides, the GO/PEG composite coated stir bar presented high thermal/chemical stability and long lifetime (>50 times). Based on it, a method of GO/PEG composite coated SBSE-HPLC-fluorescence detector (FLD) was proposed. The analytical performance of the developed SBSE-HPLC-FLD method was evaluated under the optimized conditions. The LODs for five FQs were as low as 0.0045-0.0079 ?g/L due to high enrichment factors (41.5-65.5-fold) of SBSE and high sensitive FLD. The proposed method was successfully applied for the determination of FQs in chicken muscle and chicken liver samples.(3) A molecularly imprinted polymer (MIP) coated stir bar was prepared using a self-designed polytetrafluoroethylene (PTFE) mold and in situ polymerization, with cyromazine as the dummy template for target melamine. The prepared MIP coated stir bar presented a uniform and porous surface as well as good chemical stability for melamine. Based on the mathcing pore size and recognition sites towards melamine, the MIP coating presented better selectivity to melamine (SFs:8.9) than its analogues (SFs:2.2/0.69) in methanol solution. Based on it, a method of MIP coated SBSE combined with HPLC-UV was developed for the quantification of melamine in food samples. Under the optimal conditions, the analytical performance of this method was evaluated. The LOD of the developed method was 0.54 ?g/L for melamine with an enrichment factor of 42-fold. The proposed method presented a good specific recognition ability for melamine and matrix interference resistance, and was demonstrated to be effective and sensitive for the analysis of melamine in animal food and milk samples.(4) Traditional MIPs usually suffer from incompatibility in aqueous media and low adsorption capacity, which limit the application of MIP coated stir bar in aqueous samples. To solve these problems, a water-compatible GO/MIP composite coated stir bar was prepared by in situ polymerization. The prepared water-compatible GO/MIP coated stir bar presented good mechanical strength and chemical stability. Its recognition ability (SFs:5.2) in aqueous samples was improved due to the polymerization of MIP in water environment, and the adsorption capacity for target analytes was also increased by the addition of GO in MIP pre-polymer solution. Based on it, a method of water-compatible GO/MIP coating-SBSE-HPLC-UV was proposed for the analysis of propranolol (PRO) in aqueous solution. Under the optimized conditions, the LOD of the proposed method for PRO was 0.37 ?g/L, and the EF was 59.7-fold (theoretical EF was 100-fold). The proposed method of GO/MIP coating-SBSE-HPLC-UV was successfully applied for the assay of the interested PRO drug in urine samples, and further extended to the investigation of the excretion of the drugs by monitoring the variation of the concentration of PRO in urine within 10 h after drug-taking.(5) A spiral stir bar was proposed by using stainless steel spring as the coating carrier to avoid the coating friction and increase the amount of extraction phase and thus the extraction efficiency. The stainless steel spring could be easily coated by sol-gel technique, and the coatings are filled in the cavity of the spring rather than covered on the surface of glass stir bar or stainless steel wire, resulting in a larger amount of the coatings than that coated on glass stir bar or stainless steel wire. Taking five estrogens as the model target analytes and PANi sol-gel for the coating of spiral stir bar based on ?-? interaction, hydrophobic interaction and hydrogen bonds between PANi and target estrogens, the extraction performance of spiral stir bar was evaluated. The prepared PANi coated spiral stir bar presented good extraction efficiency, good preparation reproducibility and long lifetime (more than 150 reused times) for target estrogens. Based on it, a method of PANi coated spiral stir bar sorptive extraction (sSBSE) combined with HPLC-UV was developed for the analysis of five estrogens in environmental water and animal-derived food samples..(6) A metal-organic frameworks (MOFs) incorporated monolith spiral stir bar was prepared by in-situ polymerization. MOF-5, IRMOF-3, MOF-199 and A1-MIL-53-NH2 were incorporated into poly(methacrylic acid and ethylene glycol dimethacrylate) (MAA-EGDMA) monolith, respectively. The MOF-5/monolith spiral stir bar presented high extraction efficiency for target selective serotonin reuptake inhibitors (SSRIs) due to the cavity matching, ?-? interaction, hydrophobic interaction and hydrogen bonding interaction and large surface area of poly(MAA-EGDMA) monolith. Based on it, a method of MOF-5/monolith coating combined with sSBSE-HPLC-UV was developed for the analysis of four SSRIs in urine samples. Under the optimized conditions, the analytical performance of this method was evaluated. The LODs for four SSRIs were in the range of 0.31-0.88 ?g/L, and the EFs were in the range of 75.3-120-fold (theoretical EF was 200-fold). The proposed method of MOF-5/monolith-SBSE-HPLC-UV was successfully applied for the determination of four interest SSRIs in urine samples.