Application Of UPLC-QTOF MS In Degradation Of Antibiotics And Safety Research Of Pharmaceutical Packaging Materials

Health has always been the eternal focus and pursuit of humankind.Antibiotics are widely used in various aspects of human production and life due to its wide antimicrobial spectrum,strong antibacterial activity and selectivity.However,with the excessive use of antibiotics,the problem of environmental pollution is becoming more and more serious.Because of the problems of low concentration,difficulty in handling and strong hazards,it is imperative to found a green and efficient way to deal with the pollution of antibiotics in water.In addition,plastic as the most common drug packaging materials,events that cause drug degeneration and even harm to human health occur frequently in the process of direct contact with drugs.Therefore,a stable pretreatment method for the extraction of extractables and a rapid and accurate analytical method for extractables have great significance for the inspection of the safety of pharmaceutical packaging materials.In this subject,the technology of ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-QTOF MS)and database establishment based on UNIFI software are applied to the study of photodegradation of antibiotics and the safety of drug packaging materials.A supported N-TiO2 photocatalyst was prepared to study the degradation of antibiotics and a dispersive liquid-liquid microextraction with solidification of floating organic drop pretreatment method was developed for the extraction of extractables in drug packaging materials.The main research results are as follows:1.With tetrabutyl titanate as the precursor and urea as the nitrogen source,different doping dosesage of N-Ti02 powders with visible light activity were prepared by sol-gel method and immobilized on the glass spheres with sodium silicate as binder.Through XRD,FTIR,UV-Vis,SEM,EDS,XPS and other characterization methods,it was shown that nitrogen was successfully doped into the TiO2 crystal lattice and evenly distributed on the surface of the catalyst.Also,anatase was the dominant phase in prepared N-TiO2 powders with good visible absorption activity,the catalyst was evenly distributed on the surface of the glass spheres and the morphology was unchanged before and after loading.The prepared N-TiO2 photocatalyst overcomes the problem that the pure TiO2 cannot absorb visible light and the powder catalyst is difficult to be separated and recovered,and has very important significance for the application of photocatalysis.2.With ciprofloxacin as the target antibiotic,the catalytic activity of N-TiO2 with different doping dosages was studied.UPLC-QTOF MS analysis showed that when the nitrogen element was doped to 0.34 wt%,ciprofloxacin was completely degraded after 3 h of radiation.The kinetics study showed that the degradation reaction accorded with the first order kinetic model,and the cyclic 5 experiments showed that the immobilization method was stable.By using UNIFI software,the database of ciprofloxacin degradation products(49 kinds)was established,the rapid screening and characterization of the degradation products were realized,and the degradation mechanism of ciprofloxacin was deduced.Toxicological evaluation of degradation products was carried out by T.E.S.T.software,indicating that photocatalytic degradation effectively reduced the toxicity of antibiotics.3.Using lauryl alcohol as the extractant,a dispersive liquid-liquid microextraction with solidification of floating organic drop pretreatment method was developed for the extractables of drug packaging materials.The dosage of extractant,the selection and dosage of dispersant,the extraction pH and the vortex time were optimized.The recovery experiment showed that the recovery rate of the common plastic additives was between 80%and 120%by the pretreatment method and reached the needs of analysis.The extraction method was used to treat the acid,alkaline and salt solution soaked in the plastic bottle for 90 days.The UPLC-QTOF MS data were screened by the additive library established by the laboratory,and three kinds of extractables were detected,but the content was less than 100?g/L,which accords with the requirements of the regulations.This result provides a reference for the safety research of drug packaging materials.