Cost Effective Quantification of Trace Level edta (Ethylene Di-amine Tetra Acetic Acid) by Titrimetry in Active Pharmaceutical Ingredients

Nagaraju et al
Der Chemica Sinica, 2017, 8(1):175-183
Pelagia Research Library
176
Figure 1: Chemical structure of EDTA.
Figure 2: Chemical structure of 6-APA.
Figure 3: Chemical structure of penicillin and Cephalosporin.
Figure 4: Chemical structure of Ampicillin.
Figure 5: Chemical structure of Amoxicillin.
7-ACA (7-aminocephalosporanic acid) is the core chemical structure for the synthesis of cephalosporin antibiotics and 
intermediates. It can be obtained by chemoenzymatic hydrolysis of cephalosporin C. 
In present studies, EDTA was used in preparation of drug intermediate and also the drug substance.
Titrimetric method is a convention cost effective analytical technique. The optimized titrimetric method was validated 

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Nagaraju et al
Der Chemica Sinica, 2017, 8(1):175-183
Pelagia Research Library
177
according to ICH guidelines to prove its suitability and reliability for the determination of EDTA in pharmaceutical 
drug substances during routine analysis.
Figure 6: Chemical Structure of 7-ACA (7-Aminocephalosporanic acid).
MATERIALS AND METHODS
Chemicals, reagents and samples
Analytical reagent grade of EDTA.2Na, Ammonia, Ammonium chloride, Copper sulfate from Merck chemicals, 
India. Water was distilled and purified with Millipore system (Millipore milford, MA USA), 6-Amino pencillic acid 
was provided by APL Research Centre-II(A Division of Aurobindo pharma limited).
Instrument
Auto titrator with titration vessel and ion selective electrode with reference electrode suggested system Metrohm 
titrino with electrode no:6.0502.140 and 6.0726.100.
Methods
Preparation of solutions
Preparation of Ammonia-Ammonium chloride buffer solution (pH 10): Dissolve 67.5 g of ammonium chloride in 
about 200 ml of water, add 570 ml of strong ammonia solution and dilute to 1000 ml water.
Preparation of copper sulphate solution 0.01M: Dissolve 2.5 g of copper sulphate penta hydrate in 1000 ml of water 
and standardise this solution using 50 ml of 0.1 N Standardized sodium thiosulfate solution.
Preparation of 0.1M Sodium thiosulphate: Weight and transfer about 25 g of Sodium thiosulphate and 0.2 g of sodium 
carbonate in a 1 litre volumetric flask containing 500 ml of water. Dissolve and make up to the mark with water. Allow 
to stand for 24 hours and standardize the solution.