Study On Extraction And Separation Methods Of Trace Drugs Based On Functionalized Nanocarbon Materials

With the increasing concern of drug residues in food,the extraction and separation of trace targets in complex samples have been facing higher challenges.The pharmacokinetics of new drugs need to be studied during the research and development process,so it is necessary to build quick and accurate methods for separation and analysis of trace drugs in biological samples.Based on the above comments,the selection of sample pretreatment methods is increasingly crucial.Solid phase extraction technology is one of the most widely used sample pretreatment technologies.A derivative form,called miniaturized solid phase extraction,has become a hotspot in the field of sample pretreatment because it can shorten the pretreatment time and reduce adsorbents and reagents while guaranteeing the extraction efficiency.The less amount of adsorbent in miniaturized solid phase extraction has put forward higher requirements on the performance of the adsorbent.Therefore,this paper has devoted to the development of new adsorbent materials and prepared two kinds of carbon nanomaterials.Then the adsorbents were applied to pipette-tip solid phase extraction(PT-SPE).Combined with high performance liquid chromatography(HPLC),analytical methods of trace drugs in biological matrixes were established and applied to the separation and determination of trace drugs in biological samples.Chapter one: The importance of sample pretreatment procedure in pharmaceutical analysis was briefly illustrated.The advantages and disadvantages of carbon nanomaterials and their applications in analytical chemistry were introduced in detail.Chapter two: A three-dimensional graphene/multi-walled carbon nanotubes(G/MWCNTs)composite was synthesized through the introduction of multi-walled carbon nanotubes into graphene nanosheets.The obtained composite was applied to PT-SPE cartridge and coupled with HPLC to determine estradiol in milk.The established method showed good linearity in a range of 5–250 ng m L-1 with a calibration equation Y = 6.4 × 103 X + 4.5 × 102,with the correlation coefficient(r)of 0.9998.The LOD and LOQ were 0.7 ng m L-1 and 2.3 ng m L-1,respectively.The intra-and inter-day precisions,expressed as relative standard deviations(RSDs)were 3.7% and 5.8%,respectively.The accuracy of the method was investigated by recovery experiments with milk at three spiked levels(25,100,and 250 ng mL-1),and the recoveries ranged between 88.4–110.7% with RSDs ≤ 7.4%.Chapter three: On the basis of the former composite,a new adsorbent was synthesized via the introduction of an amine-terminated ionic liquid onto G/MWCNTs.The obtained ionic liquid-graphene/multi-walled carbon nanotubes composite material has better performance and more kinds of interactions towards analytes.Applied to PT-SPE cartridges and coupled with HPLC-UV,the ionic liquid-graphene/multi-walled carbon nanotubes composite was used to determine(Z)-3-(chloromethylene)-6-fluorothiochroman-4-one in urine.Good linearity of the developed method was achieved in a range of 0.03–5.0 μg m L-1 with a calibration equation Y = 7.7 × 104 X + 2.8 × 102,and r = 0.9999.The LOD and LOQ were 9 × 10-3 μg mL-1 and 3.0 × 10-2 μg m L-1,respectively.The intra-and inter-day precisions were 4.8% and 5.5%,respectively.The accuracy of the proposed method was investigated by recovery experiments with urine at three spiked levels(0.1,0.5,and 1.0 μg m L-1),and the recoveries ranged between 73.9-93.9% with RSDs ≤ 7.8%.