Multivariate Calibration Methods For Quantitative Analysis Of Antineoplastic Drugs And Biological Macromolecules In Complex Matrices

Multiway calibration methods based on multilinear components models have gaining more and more attention in the field of analytical science. Using the "mathematical separation" to assist or substitute for physical and chemical separation, which will enable one to achieve direct quantitative analysis of multiple analytes of interest in complex systems even in the presence of unknown interferents. The "second-order advantage" provides a new idea in the determination of multiple substances simultaneously. Along with the rapid development of analytical instruments and computer technology, second-order calibration methods combined with different types of detecting techniques have realized the determination of analytes of interest in complex matrics, such as medicine, food, cosmetics, and environmental samples and so on. At present, the optimization of many major diseases (cancer, cardiovascular disease, or rheumatism) treatment is particularly important. Therefore, the author combines the multiway calibration method with different instrumental analysis for quantitative analysis of some drugs and biological macromolecule in the different matrics based on the understanding of the theoretical knowledge of second-order calibration, and further explores the interaction mechanism of procaine (PRO) and human serum albumin (HSA). The main contents are as follows:Chapter 2:Three dimensional calibration-assisted HPLC-DAD method for rapid determination of four kinds of tyrosine kinase inhibitors in human plasmaTyrosine kinase is the key regulator of cell growth、proliferation and differentiation. Many serious diseases such as cancer and rheumatoid arthritis were found that the regulation of the kinase signal is abnormal. The study found that the tyrosinase mediated signal transduction is closely related to the occurrence and development of tumor. Therefore, the treatment of the cancer can be effectively treated by blocking the signal transduction pathway. Vandetanib, pazopanib, afatinib and dasatinib are four different kinds of tyrosine kinase inhibitors, and have been approved for the treatment of medullary thyroid carcinoma, renal cell carcinoma, leukemia and so on. The proposed method that combining alternating trilinear decomposition (ATLO) algorithm with high performance liquid chromatography with diode array detection (DAD) successfully achieved quantitative analysis of vandetanib, pazopanib, afatinib and dasatinib in seven different human plasma samples. This method possesses desirable features in terms of rapidity, high sensitivity and effectivity.Chapter 3:Quantitative analysis of three kinds of anticoagulant drugs in human body fluids and active substances in Shaaban tablets using second-order calibration combined with HPLC-DAD methodRivaroxaban, apixaban and dabigatran are the new oral anticoagulants. Compared with traditional anticoagulants, such as heparin, hirudin, recombinant hirudin, argatroban and vitamin K antagonist warfarin and so on, the new oral anticoagulants barely affected by food and drug. This work has successfully realized the quantitative analysis of three kinds of anticoagulant drugs in human body fluids and active substances in Shaaban tablets by using ATLD combined with HPLC-DAD method. The proposed method is simple, economic, time and labor saving, and keeps good accuracy and repeatability. It is expected to develop as a new method for quality control of drug production and real-time monitoring the blood concentration of drugs.Chapter 4:Determination the indomethacin content in complex matrix using intrinsic fluorescence combined with second order calibration methodIndomethacin, is a non-steroidal anti-inflammatory drug, which can inhibit the synthesis of cyclooxygenase to reduce the generation of prostaglandins, and leading to remarkable antipyretic, analgesic and anti-inflammatory functions. This work adopted a strategy that combined three-dimensional fluorescence with PARAFAC to realize the determination of indometacin in human plasma, urine, and indometacin enteric coated tablet. Even the fluorescence spectra of analyte of interest almost completely overlap with that of background interferent. "mathematical separation" insteads of the traditional physical and chemical separation can simplify experimental process, avoid complex sample pretreatment, and improve accuracy of the analysis method.Chapter 5:Multiway calibration method combining with 3D fluorescence spectrum for quantitative analysis of human serum albumin and studying the interaction between procaine and human serum albuminHuman serum albumin (HSA), as a common soluble protein of internal circulation system of human body, plays an important biochemical role. Studying the interaction mechanism of small molecule drugs and serum albumin will contribute to the understanding of absorption, distribution, metabolism and excretion of the drug. Usually, the weak binding force makes high plasma concentration of drug, in consequence, the efficacy of drug will be strong and fast. Conversely, the strong acting force causes low blood concentration of drug, which leads to a longer acting time and a slower metabolism, This behavior is related to the chemical structure of drugs and the way of drug administered. Therefore, the research of binding mechanism between drugs and HSA is of importance for the development of pharmaceutical and pharmacodynamics. The presented work combined a three-dimensional fluorescence with second-order calibration method for the determination of the free HSA concentration in hybrid dynamic system. The exploration in terms of the influence of temperature on the interaction of HSA and PRO has been realized using the four-way calibration method.