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تطبيق الكيمومترية في تقدير بعض العقاقير بطرائق تحليلية مختلفة == Application of Chemometrics in Determination of Some Drugs via Different Analytical Techniques
Author name:
نهلة عبد الرحمن علي العساف
Supervisor name:
سرمد بهجت ديكران | علاء كريم محمد
General topic:
Chemistry
Specific topic:
Chemistry
Degree:
Doctorate
University:
University of Baghdad
Language:
English
University location:
Baghdad
First pages:
25T1864 - p.pdf
Abstract:
The work incorporated in the thesis is an attempt to develop new analytical methods for the determination of four medications belonging to different therapeutic groups namely; furosemide (FURO), carbamazepine (CARB), diazepam (DIAZ) and carvedilol (CARV). The study, which included the estimation of the studied drugs in their pure forms and in pharmaceutical formulations (tablets, ampoule and oral suspension), has been described in four chapters as follows : Chapter one : Includes an introduction to chromatography as well as basic principles, classification and theory of chromatography. A brief account on basic principles, modes and instrumentation of high performance liquid chromatography have been reported. The basic principles of derivative spectrophotometry and partial least squares method have been described as well as their applications in pharmaceutical analysis. In addition, this chapter gives a brief description of systematic name, structure and literatures on different methods reported for FURO, CARB, DIAZ and CARV.Chapter two : Covers the experimental part that includes chemicals, solvents and instruments used throughout this work as well as the description of the preparation of standard stock solutions and buffer solutions.Chapter three : Depicts the development and validation of a simple reverse - phase high performance liquid chromatographic method for the simultaneous analysis (separation and quantification) of furosemide, carbamazepine, diazepam and carvedilol.The effect of various factors such as mobile phase composition, flow rate, organic modifier and buffer percentage, pH of buffer, temperature and injection volume on the chromatographic performance of the four analytes have been studied. Under optimum conditions, isocratic elution with flow rate of 1.5 mL.min - 1 was employed on RP - NUCLEODUR® 100 - 5 C18ec (250 x 4.6 mm, 5μm) column. TheSummaryIImobile phase composed of 50 : 50 acetonitrile : deionized water (pH 3.6, acidified with acetic acid), the column temperature was 40°C and the injection volume 10 μL. The detection was done with UV detector at 226 nm, and the order of elution were FURO, CARB, DIAZ and CARV at 1.90 min, 2.79 min, 5.39 min and 9.56 min respectively. Calibration curves were constructed by plotting the peak area and the peak height against corresponding concentrations in the range of 1.0 - 100.0 μg.mL - 1 for furosemide, 2.5 - 100.0 μg.mL - 1 for both carbamazepine and diazepam and 5.0 - 100.0 μg.mL - 1 for carvedilol. The LOD and LOQ for the cited drugs were between (0.115 - 0.950 μg.mL - 1) and (0.348 - 1.440 μg.mL - 1) for peak area and (0.074 - 2.877 μg.mL - 1) and (0.225 - 1.599 μg.mL - 1) for peak height respectively. The precision in term of relative standard deviation was calculated and found to be less than 4 %, and accuracy expressed as relative error was less than 5%.The developed method has been applied successfully for the determination of the cited drugs in their pharmaceutical preparations and the recovery % were found to be (102.3% - 106.6%) and (97.5% - 103.0%) for furosemide, (94.2% - 98.2%) and (88.8% - 94.0%) for carbamazepine, (98.4% - 102.9%) and (96.9% - 107.5%) for diazepam, (92.3% - 106.4%) and (93.8% - 106.6%) for carvedilol for peak area and peak height respectively.Chapter four : Entitled “simultaneous determination of furosemide, carbamazepine, diazepam and carvedilol” deals with the simultaneous estimation of the four drugs in their quaternary mixtures via two methods namely : partial least squares regression and derivative spectrophotometry.Partial least squares (PLS) method was used as chemometric technique for simultaneous spectrophotometric estimation of FURO, CARB, DIAZ and CARV in their quaternary mixtures. Calibration graph for each drug was constructed in the concentration range of (1 - 20 μg.mL - 1) at 233.0 nm, 215.0 nm, 228.5 nm and 242.5 nm for FURO, CARB, DIAZ and CARV respectively and linear relations were obtained inSummaryIIIstudied concentration ranges. The first step in PLS methodology involved constructing a calibration (training) set from the spectrophotometric data obtained by careful UV - measurements on a set of known samples, composing of 84 mixtures that selected according to Simplex Lattice Mixture Design.The absorbance data matrices corresponding to the concentration data matrices for each of the 84 mixtures were obtained by the measurements of absorbance in the range 200 - 350 nm with a scan speed of 10 nm.sec - 1, averaging of 1.0 nm, bandwidth of 1.8 nm, and data interval of 0.5 nm against solvent blank. The PLS - 1 and PLS - 2 regression models were built with the help of OriginPro software version 2015 program and the concentration of the four drugs were then predicted. The result of relative standard deviation percentage (RSD %) and relative error percentage (RE %) were in the ranges (1.2638% - 6.0529%) and ( - 0.0845% - 3.8053%) respectively. The proposed method was successfully applied in the simultaneous determination of furosemide, carbamazepine, diazepam and carvedilol in their synthetic sample mixtures.Derivative spectrophotometric techniques (first, second, third and fourth derivatives) were developed for the simultaneous determination of FURO, CARB, DIAZ and CARV in their quaternary mixtures. It was found that FURO and CARV could be determined by all modes of derivative (i.e. first to fourth order); CARB could be determined by first, second, and third order; while only first and second modes of derivative could be used in the determination of DIAZ in presence of other investigated drugs.The zero crossing technique was employed in first derivative measurements, using the peak height to baseline at 336.5, 358.5, 306.0 and 331.5 nm for CARV, FURO, CARB and DIAZ respectively, which was in proportion to the drug concentration therefore they are used for the quantitative estimation of the titled drugs. The second derivative spectra of the same mixtures show that peak height at332.5 nm for CARV, and height to baseline at zero cross (273.5, 226.0 and 218.5 nm) for FURO, CARB and DIAZ respectively, could be used to quantify the corresponding concentration for each drug. While in the third derivative method the peak height at 288.0 nm and height to baseline at zero cross at 237.5 and 224.0 nm were found to be useful for the determination of CARV, FURO and CARB respectively. The careful inspection of the fourth derivative spectra obtained for the mentioned quaternary mixtures reveal that peak height at 288.0 nm and height to baseline at zero cross at 234.0 nm were in proportion to the CARV and FURO concentrations respectively.The results show no interferences from the excipients on the determination of the four drugs by utilizing these techniques, thus they were suitable to be applied for the estimation of CARV, FURO, CARB and DIAZ in their pharmaceutical preparations.
