I= DEVELOPMENT OF NEW ANALYTICAL METHODS FOR 4-QUNIOLONE ANTIBACTERIALS AND CEPHALOSPORIN ANTIBIOTICS
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Title of Thesis
DEVELOPMENT OF NEW ANALYTICAL METHODS FOR 4-QUNIOLONE ANTIBACTERIALS AND CEPHALOSPORIN ANTIBIOTICS

Author(s)
Amber R. Solangi
Institute/University/Department Details
National Centre of Excellence in Analytical Chemistry/ University of Sindh
Session
2007
Subject
Chemistry
Number of Pages
177
Keywords (Extracted from title, table of contents and abstract of thesis)
nalidixic acid, 4-quniolone antibacterials, cephalosporin antibiotics, 7-aminocephalosporanic acid, cefadroxil monohydrate, cefixime, cefuroxime sodium, ceftriaxone sodium, ceftizoxime sodium, cefaclor, cefradine, cefotoxime sodium, ofloxacin, pipemidic acid, ceftizoxime, ceftriaxone, paracetamol, diclofenac sodium, norfloxacin, diclofenac sodium, oxytocin

Abstract
Quinolones are a series of synthetic antibacterial derived from nalidixic acid while cephalosporin ring structure is derived from 7-aminocephalosporanic acid (7-ACA). They are bactericidal drugs with both gram-positive and gram-negative activity. They inhibit bacterial cell wall synthesis in a way similar to the penicillin. They are widely distributed to most body fluids and tissues with concentrations that are generally sufficient to treat infection, especially in the presence of inflammation (which. enhances diffusion). Because many of these drugs are well absorbed after oral administration, they are clinically useful in the outpatient setting. They are widely prescribed for the treatment of infectious diseases in humans as well as in animals.

Several methods are reported for the determination of these drugs including spectroscopic and chromatographic. It has been reported that Quinolones and B-lactam have some electrochemical activity. Therefore voltammetric methods have been explored for the analysis of these drugs. Fast, versatile and precise voltammetric methods had been developed for four Quinolone antibacterial and four cephalosporin antibiotics using differential pulse cathodic stripping voltammetric mode. The drugs included in the study were Pipemidic acid, Norfloxacin, Enoxacin and Ofloxacin from Quinolone group and Cefadroxil, Cefuroxime, Ceftazidime and Ceftizoxime from cephalosporin group. Different instrumental and chemical parameters have been optimized for each drug individually. Each drug reduces at a characteristic peak potential. The peak potential for Pipemidic acid is -750mV, for Norfloxacin -1080mV, for Enoxacin -980mV, for Ofloxacin 1150mV, for Cefadroxil is - 750mV, for Cefuroxime is - 550mV, for Ceftazidime is -600 mV and for Ceftizoxime is -165mV. The resulted peak current vs potential voltammogram were used for the interpretation of desired qualitative and quantitative information of each drug. The interferences study was done using different additives. No significant interference is observed for any drug. The detection limit for the drugs-were found to be 0.1 µg/ml for Pipemidic acid, 50 ng/ml for Enoxacin, 1 µg/ml for Ofloxacin, 10 µg/ml for Norfloxacin, 0.1 µg/ml for Cefadroxil, 1 µg/ml for Cefuroxime, 50 ng/ml for Ceftazidime and 50 ng/ml for Ceftizoxime. The developed methods were successfully applied for the determination of antibiotic drugs in commercially available capsules/tablets and in biological fluids (human blood serum and urine) with good recoveries.

In second part of the study, Capillary Electrophoresis (CE) has been employed for the qualitative and quantitative study of quinolones, cephalosporins, anti-inflammatory, analgesics and vitamins. CE has proved to be a powerful technique for the analysis of pharmaceuticals. It is used in many industrial pharmaceutical companies and applications including the determination of related impurities, main component assay and drug residue analysis. Because CE is still a rapidly developing technique, many developments and applications appear year by year.

Five different methods have been developed using CE. In first method the eight most frequently used cephalosporins antibacterial drugs have been separated and analyzed by means of Capillary Electrophoresis (CE). A mixture of cephalosporins (more than one antibiotic at the same time) is generally not used in medicine. The reason to study a great number of drugs was to prove the applicability of CE for the analysis of pharmaceuticals in general.

A simple, accurate and rapid method for the separation and simultaneous determination of eight cephalosporin of different generations: cefadroxil monohydrate, cefixime, cefuroxime sodium, ceftriaxone sodium, ceftizoxime sodium, cefaclor, cefradine and cefotoxime sodium in a mixture has been developed using capillary electrophoresis. Factors affecting the separation were pH and concentration of buffer, injection time and applied voltage. Separations were carried out in less than 11 min with a 0.05M sodium tetraborate buffer, pH 9.0. The carrier electrolyte gave baseline separation with good resolution, great reproducibility and accuracy. Calibration plots were linear over at least three orders of magnitude of analyte concentrations, the lower limits of detection being within the range 1 - 3 µgml-1 Detection was performed by DV absorbance at wavelengths of 250 nm. The method was validated for the analysis of cephalosporins in pharmaceutical preparations and in urine sample.

Second method has been developed for seven structurally different drugs; two quinolone antibacterial drugs: ofloxacin, pipemidic acid in combination with analgesic, anti-inflammatory drugs and vitamins. Separation was carried out in less than 9.0 min with a 0.05M sodium tetraborate buffer, pH 10. Detection was performed by DV absorbance at wavelengths of 230 nm. The method was validated for the analysis of drugs in pharmaceutical preparations and in urine samples.

Third method has been developed for determination and separation of four different drugs; Ceftizoxime, Ceftriaxone, Paracetamol and Diclofenac sodium. Separation was carried out in less than 8.0 min with a 0.05 M sodium tetraborate buffer, pH 9.0. Detection was performed by DV absorbance at wavelengths of 214 nm. The method was validated for the analysis of drugs in pharmaceutical preparations and in human blood serum.

Fourth method has been developed for the determination of Ciprofloxacin with paracetamol and diclofenac sodium. Separation was carried out in less than 7.0 min with a 0.05M sodium tetraborate buffer, pH 9.0. Detection was performed by DV absorbance at wavelengths of 260 nm. The method was validated for the analysis of drugs in pharmaceutical preparations and in urine samples.

Fifth method has been developed for the determination of Norfloxacin with diclofenac sodium and oxytocin. Separation was carried out in less than 9.0 min with a 0.05M sodium tetraborate buffer, pH 10. Detection was performed by DV absorbance at wavelengths of 220 nm. The methods were validated for the analysis of drugs in pharmaceutical preparations and in buffalo milk samples.

Download Full Thesis
2653.03 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
240.18 KB
2 1 Introduction 1
549 KB
  1.1 Antibiotics 1
  1.2 4-Quinolones 9
  1.3 Cephalosporins 21
3 2 Literature Review 46
217.83 KB
  2.1 4-Quinoloen Antibacterial 46
  2.2 Cephalosporin Antibiotics 53
4 3 Materials And Methods 65
49.72 KB
  3.1 Chemical And Reagents 65
  3.2 Antibiotic Standard 65
  3.3 Stock Solutions 65
  3.4 Supporting Electrolytes 65
  3.5 Va Trace Analyzer 66
  3.6 Ph Meter 66
  3.7 Analytical Procedure 66
  3.8 Procedure For Analysis Of Pharmaceutical Formulations 67
  3.9 Procedure For Analysis Of Biological Fluids (Human Urine ) 67
  3.10 Procedure For Analysis Of Biological Fluids (Human Blood Serum ) 68
5 4 Results And Discussion 70
523.13 KB
  4.1 Adsportive Stripping Voltammetric Determination Of Norfloxacin And Enoxacin In Pharmaceuticals 70
  4.2 Determination Of Pipemidic Acid And Ofloxacin In Pharmaceutical Dosages And In Human Urine By Cathodic Stripping Voltammetry 78
  4.3 Cathodic Stripping Voltammetric Determination Of Cefadroxil In Pharmaceutical Preparations And In Blood Serum 87
  4.4 Voltammetric In Pharmaceuticals Dosages And In Urine Samples 93
6 5 Conclusion 104
32.56 KB
7 6 Materials And Methods 106
81.62 KB
  6.1 Chemicals And Reagents 106
  6.2 Drug Standards 106
  6.3 Buffer Electrolytes 106
  6.4 Stock Standard Solution 107
  6.5 Instrumentation 107
  6.6 Regeneration Of Capillary 107
  6.7 Analytical Procedure 108
  6.8 Procedure For Pharmaceutical Analysis 108
  6.9 Procedure For Urine Samples 108
  6.10 Procedure For Blood Serum 109
  6.11 Procedure For Milk Samples 109
  6.12 Data Manipulations 110
8 7 Results And Discussion 112
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  7.1 Simultaneous Determination Of Eight Cephalosporin Antibiotics In Pharmaceuticals And In Human Urine Samples 112
  7.2 Simultaneous Determination Of Seven Structurally Different Drugs In Pharmaceuticals And In Human Urine Samples 125
  7.3 Simultaneous Analysis Of Ceftriamone , Ceftizoxime , Paracetamol And Diclofenac Sodium In Pharmaceuticals And Human Blood Serum 140
  7.4 A Rapid Method For Quanitation Of Ciprofloxacin, Paracetamol And Diclofenac Sodium In Pharmaceuticals And Human Urine Samples Using Capillary Electrophoresis 151
  7.5 Separation And Quantitation Of Norfloxacin , Oxytocin And Diclofenac Sodium In Pharmaceuticals And In Milk Samples Using Capillary Electrophoresis 119
9 8 Conclusion 175
191.83 KB