The Study Of Quantitative Analysis Method For Propofol And Application Of Boron Nitride Quantum Dots In Dopamine Detection

Contemporary medicine increasingly relies on drug research.Accordingly,the monitoring of drugs in biological samples has become more and more important.Therefore,the establishment of simple,rapid and sensitive detection methods to detect drugs is of great significance for disease prevention,diagnosis and clinical decision-making.At present,a series of drug analytical techniques have been developed to improve clinical administration strategies,and to deepen the understanding of drug pharmacokinetics,pharmacodynamics and metabolism,so as to make their clinical application more effective.The purpose of this paper is to explore the interference and influence of ginseng or other Chinese herbal medicines on the anesthetic effect of propofol during anesthesia in clinical,therefore,the quantitative approaches for propofol determination are developed.In addition,the detection method for dopamine(DA)is studied.The experiment is accomplished well by means of the establishment of highly sensitive detection platform.Starting from the traditional UPLC-MS/MS method,novel detection systems are established based on electrochemiluminescence(ECL)and fluorescence,which are applied to the high-sensitivity detection and analysis of drugs in biological samples.In preface part,we firstly give a briefly review to the commonly used pharmaceutical analytical methods,and introduce the current frequently used detection methods for propofol and DA.Subsequently,specific research work was elaborated from the following three aspects:(1)To investigate the effect of ginsenoside Rb₁ on propofol in vivo,the concentrations of propofol with or without oral administration of ginsenoside Rb₁ in vivo were compared by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)for the first time.Chromatographic analysis was carried out using a BEH C18 column by gradient elution using acetonitrile and0.05‰aqueous ammonia as the mobile phase at a flow rate of 0.3 m L/min and thymol as an internal standard.The multiple reaction monitoring(MRM)transitions of m/z 177?161 and m/z 149?133 were used to monitor propofol and thymol,respectively.The method was validated for determination within the concentration range 100-10000 ng/m L.A significant effect of ginsenoside Rb₁ administration on the pharmacokinetics of propofol was observed.The C_max and AUC_0-t in plasma was reduced following the oral administration of Rb₁,with significantly increased V and CL.These findings demonstrated that ginsenoside Rb₁ promoted the distribution and elimination of propofol.Therefore,ginsenoside Rb₁combined with propofol in clinical treatment may exhibit potential interactions,and people should pay attention to the combined treatment of propofol with perioperative Rb₁-containing herbal medicines or supplements.(2)At present,the UPLC-MS/MS method is widely used in drug analysis and detection,however,it still has certain limitations.For instance,sufficient sample preparation steps are required to separate drugs and their metabolites from the matrix,the instrument operation is complicated,and high cost is required.In order to solve these problems,a new facile method for determination of anesthetic drug propofol based on quenching of ECL was presented.When propofol was introduced to tris(2,2'-bipyridyl)-ruthenium(II)/tripropylamine(Ru(bpy)₃²⁺/TPr A)system,an obvious decrease of ECL signal was observed due to the energy transfer between the excited state of Ru(bpy)₃^2+*and the electro-oxidation products of propofol.Under optimum conditions,the inhibited ECL response was linearly with the propofol concentration in the range of 20 ng/m L-8000 ng/m L with a detection limit of 10ng/m L(S/N=3).Moreover,the proposed sensing platform showed good reproducibility with relative standard deviation of 5.56%for 5?g/m L propofol(n=5).Finally,the proposed method was applied for detection of propofol in human serum with a satisfactory recovery.As a sensitive,rapid,simple and cost-effective method,the sensing platform holds great potential in determination of propofol.The method could be utilized to investigate the interference and influence of ginseng or other Chinese herbal medicines on the anesthetic effect of propofol in human body.(3)Although the ECL method is highly sensitive,it is susceptible to interference from the testing environment.Fluorescence detection method has attracted wide attention due to its advantages such as high sensitivity and selectivity,simple operation and small amount of sample required.The research group constructs a DA detection platform based on the catalytic properties and fluorescence quenching effect of boron nitride quantum dots(BNQDs).Monitoring DA concentration is vital for preventing and diagnosing DA related diseases.Optical probes of BNQDs were first revealed as the catalysts for polymerization of DA in the co-existence of Cu²⁺.The formation of polydopamine(PDA)induced the fluorescence quenching of BNQDs,which provides the basis for DA analysis.In contrast with the traditional sensing principle of DA,where direct or indirect influence on the optical probes were often adopted,a new sensing concept was disclosed owing to the in-situ formed PDA originating from the synergetic effect between BNQDs and Cu²⁺.In the co-presence of BNQDs and Cu²⁺,DA was catalytically oxidized to PDA,accompanied with obvious color change from colorless to brown.Different from the previous reports where BNQDs were employed as the optical probe,herein,BNQDs not only acted as the optical energy donor,but also as the catalysts for the formation of PDA.The quenching efficiency due to the inner filter effect and the electron transfer between BNQDs and PDA was directly proportional to the concentration of DA linearly ranging from 2 to 80?M with a limit of detection of 0.49?M.The present system exhibited outstanding selectivity for DA among other interfering coexisting biomolecules.And the practical application of proposed platform was verified in the assay of DA in human plasma samples,with satisfied recoveries scaling from101.24%to 111.98%.With the satisfied reliability,repeatability and stability,the proposed simple sensor showed great potential for DA detection in other biomedical applications.