Second-order Calibration Methods Applied To Determination Of Clinically Commonly-used Drugs And Stimulants In Human Body Fluid Samples

Both the abundant appearance of modern analytical instruments and thepopularization of computer promote fundamentally the rapid development ofchemometrics, especially multivariate resolution and calibration methods which havebecome an international research focus by their unique advantages. Due to thecapability of mathematical separation, second-order calibration is combined withinstrument analysis to determine rapidly and directly concentration of the componentsin complex background, which can be used to solve practical problems in analyticalchemistry. This paper is focused on research of pharmaceutical analysis in humanbody fluids, such as serum and urine. Second-order calibration methods coupled withthree-dimensional fluorescence spectroscopy technology or high-performance liquidchromatography-diode array detection (HPLC-DAD) were used for simultaneousdetermination of some drugs in the human body fluids, even in the presence ofunknown interference. Satisfactory qualitative and quantitative results had beenobtained, which suggested the proposed strategy was justifiable and viable. Theresearch interests mainly include:1. Excitation-emission fluorescence spectroscopy combined with alternatingtrilinear decomposition (ATLD) method was applied in the determination of pipemidicacid in human plasma and urine samples. In clinical pharmacology, bioavailability ofpipemidic acid is obtained by monitoring its concentration in blood or urine throughdifferent periods after taking the drug. However, a fundamental problem in traditionalfluorescence method is the serious overlapping spectrum between pipemidic acid andserum background. The method proposed in this chapter was based on the the idea ofmathematical separation to overcome the shortcomings of traditional fluorescencemethod. Without tedious chemical separation, this method can also determinequantitatively the target analytes in urine and plasma samples under the disturbance ofspectral overlapping, which provide a reference for instructing its clinicalpharmacology study and rational drug use in clinic.2. As one of the most common constitutional anesthetics and sedatives, propofolmay involve in the suppression of memory and ligustrazine may improvepropofol-induced learning deficit and dysmnesia. In addition, ligustrazine andpropofol in composite exerts the protective effect on ischemia-reperfusion damaged liver. Therefore, monitoring the propofol and ligustrazine in human plasma is of greatsignificance in clinic. However, there is heavy overlapping among the fluorescencespectra of the two analytes and the natural interferences in the complicated serumowing to wide-band characteristic of fluorescence spectrum, which fails thetraditional fluorescence spectroscopy. In this chapter, a novel strategy that integratinga three-dimensional response matrix constituted by excitation-emission fluorescencespectra with parallel factor analysis (PARAFAC) method was put forward to realizethe simultaneous determination of propofol and ligustrazine in human plasma samples,which exploits the "second-order advantage" to solve the the problem of overlappingspectra among the analytes and background.3. In spite of the advantage of being highly sensitive, simple and rapid, when thefluorescence method is applied in the simultanous determination of ligustrazine andferulic acid in plasma, there is serious interference of both the matrix-based substanceand mutual disturbance between ligustrazine and ferulic acid. In this chapter,simultaneous determination of ligustrazin and ferulic acid in human plasma sampleswas achieved by combining excitation-emission matrix fluorescence withsecond-order calibration method based on ATLD algorithm. This method avoids oftedious extraction and separation steps and overcomes the problem caused by seriousfluorescence signal overlapping between analytes and plasma matrices. Reliableresults were obtained, which means that a new underlying method for monitoring themetabolism of ligustrazine and ferulic acid in human plasma.4. A simple strategy to ascertain plasma concentration of salbutamol andterbutaline was put forward in this chapter, the recorded HPLC-DAD data wasanalyzed by ATLD method. This approach fully exploited “second-order advantage”,namely exact quantification of substance of interest could be achieved even in thepresence of uncalibrated interferents. The combination of HPLC-DAD with ATLDapplied in simultaneous determination of salbutamol and terbutaline in plasmasamples can overcome the complication of heavily overlapped peaks between analytesand matrix-based ingredients. At the same time, subsection division strategy wasintroduced to surmount the weakness of the inherently almost identical spectralprofiles rooted in structural similarity between the two analytes. With the simplestchromatographic condition and fewer pretreatments, this method saves lots ofexperimentation.5. An ingenious integration of HPLC-DAD with second-order calibration methodbased on ATLD algorithm was presented in this chapter, which enabled simultaneous determination of seven beta blockers in serum samples with fewer pretreatments andsimpler chromatographic condition. Despite of the intricate matrix effect, this methodachieved the direct qualitative and quantitative analysis of interested componentseven in the presence of unknown interferences. Compared with traditionalchromatographic methods, this approach is appealing in terms of simpledeproteinisation in plasma samples, freedom from laborious and time-consumingpre-column preparations, no need of internal standards, short elution time in isocraticmode.