High-order Calibration For Quantitative Analysis In Complex Systems And Studies Of The Interactions Between Small Drugs And HSA

The chemometrics is a powerful analytical tool for complex systems studies,high-order calibration which is a important part of chemometrics uniquely decomposethe linear data by replacing or partially replacing the traditional “physical andchemical separation” with “mathematical separation”, and directly quantify thecomponent（s） of interest in presence of co-exist substance in the complex systems.With the complexity of the measurement system and the diversification ofmeasurement information, high-order calibration methodologies combined with thetechnology of modern analytical instruments used in a complex research system willembrace a broad application prospect. The author did some reseaches in the field ofapplications of the high-order calibration methods in chemometrics, the main contentsare as follows:In Chapter2, a novel approach for simultaneous quantitation of acridine orange,acriflavine and fluorescein in the different type of cell culture medium samples usingexcitation-emission matrix fluorescence （EEM） and second-order calibration strategybased on parallel factor analysis （PARAFAC） algorithm was employed. In vitrostudies, when used to track cell growth, locate intracellular feature and quantitifyintracellular substances, the fluorescence spectrums of acridine orange （ADO）,acriflavine （AF） and fluorescein （FC） are commonly overlapped with the systembackground （such as cell culture mediums）. In spite of natural fluorescence yielded bymany components in cell culture, the resolved excitation and emission spectrumacquired by PARAFAC algorithm completely overlaid on representative the actual.The satisfactory quantitative results indicated that the developed method can fast ly,directly, simultaneously predict the concentrations of the analythes in the three cellculture medium samples.In Chapter3, citalopram （CIT）, fluoxetine （FLU） and paroxetine （PAR） arecommonly used to treat depression. Because of their natural fluorescence properties,an effective approach was developed for the simultaneous determination of CIT, FLUand PAR in human plasma samples by the incorporation of excitation-emissionfluorescence （EEM） and second-order calibration method based on the parallel factoranalysis （PARAFAC） algorithm. Even though the spectra of the target analytesseriously overlapped with the spectral of the uncalibrated interferences, the accurate quantification of individual components of interest were directly accomplishedwithout previous separation procedure, exploiting the “second order advantage”.In Chapter4, the cryptotanshinone （CTS）, tanshinone I （TS Ⅰ） and tanshinoneIIA （TS ⅡA） are hydrophobic active components of Salvia, a analytical method hasbeen established for simultaneous determination of them in Radix SalviaeMiltiorrhizae and Fufang Danshen tablet samples. The second-order calibrationmethod based on self-weighed alternating trilinear decomposition （SWATLD）algorithm was presented to treat the data from high performance liquidchromatography-diode array detection （HPLC-DAD）. Although simple mobile wasselected, we successfully achieved the purpose of rapid and accurate quantitativeanalysis regardless of co-eluting components and overlapping spectra. This strategy,which provides an application reference for the analysis in drug quality control, couldsimplify the chromatographic conditions, save analysis time and improve workefficiency. Moreover, it was not necessary for a complete separation between theanalyte（s） and the background.In Chapter5, antibiotics which were excessively produced and abused by manypatients unknowingly had potential hazards on the ecological environment. Thus, theelimination and residue analysis of antibiotics in environment have attractedincreasing attentions as a concerned theme. Ofloxacin （OFL） and danofloxacin （DAN）were widely used in daily life, hydrolysis （photodegradation included） is a significantfate in surface waters after they entered environment. However, OFL ans DAN cannotbe effectively removed in a short time by photodegradation under natural conditionsbecause the contaminants do not readily absorb photons at wavelengths present insunlight. UV/H₂O₂advanced oxidation technology has unique advantages for thetreatment of refractory derived organic matter. In this study, OFL and DAN in pH3.0aqueous systems with UV/H₂O₂advanced oxidation process have been investigated bykinetic-spectrophotometric coupled with high-order （second-and third-order）calibration chemometric methods which were presented in the photochemical kineticsand simultaneous quantitative analysis of the two antibiotics. The spectra of the twodrugs as well as the co-existing species in reaction process can be directly andconveniently obtained without any pretreatment procedure regardless of the excitationand emission profiles heavily overlapped with each other in the presence ofuncalibrated interfering components in complex background. The satisfactory ofquantitative estimation confirm that the chemometrics-based protocol was establishedfor a sensitive, accurate, fast and effective analysis method in practical applications of environment monitoring.In Chapter6, the investigation for the interaction between salicylic acid （SA）and human albumin （HSA） in pH7.4Tris-HCl buffers with the use ofexcitation-emission matrix fluorescence coupled with second-order calibrationmethodology based on parallel factor analysis （PARAFAC） algorithm was proposed.The quenching mechanism of HSA by SL was been found to been static quenching,the Stern-Volmer quenching constant KSV, the binding sites number n and the bindingconstant K were calculated in the aid of second-order calibration method. Competitiveexperiments using site markers, warfarin for site I and ibuprofen for site II, indicatedthat SA was possible to be binded to site I but at a different location from the bindingsite for warfarin.