Dr Pramod Kumar Pandey BSc (Hons), MSc, PhD, founder of PharmaGuru.co, is a highly experienced Analytical Research Expert with over 31 years in the pharmaceutical industry. He has played a key role in advancing innovation across leading Indian and global pharmaceutical companies. He can be reached at admin@pharmaguru.co
In Complexometric titration, complex formation takes place during the titration. A typical example is EDTA titration. Several titration techniques are used in the pharmaceutical industry, and one them is EDTA titration. It plays a key role in determining metal ion concentrations. This method is highly valued for its specificity, accuracy, and applicability across a range […]
What Is Complexometric Titration or EDTA Titration: Get Matery in 3 Minutes With 3+ FAQs
In Complexometric titration, complex formation takes place during the titration. A typical example is EDTA titration.
Several titration techniques are used in the pharmaceutical industry, and one them is EDTA titration. It plays a key role in determining metal ion concentrations. This method is highly valued for its specificity, accuracy, and applicability across a range of pharmaceutical formulations and raw materials.
EDTA Titration (Source: Bing)
Major Takeaway: FAQs
What does EDTA do in titration?
During the reaction, EDTA displaces the indicator by forming a more stable complex with the metal ion. Once the reaction is complete, a color change is observed, corresponding to the color of the free indicator ligand at the given pH.
What is the principle of EDTA?
The principle of EDTA titration is based on the formation of a stable, water-soluble complex between EDTA (a chelating agent) and metal ions in solution. EDTA binds metal ions in a 1:1 ratio, and the endpoint is detected using a metal ion indicator that changes color when the metal ion is completely complexed by EDTA.
Which indicator is used for EDTA titration?
Eriochrome Black T is commonly used as the indicator in EDTA titration.
What is Complexometric or EDTA Titration?
Complexometric titration is a form of volumetric analysis where the formation of a complex compound between a metal ion and a chelating agent (ligand) is used to determine the concentration of the metal ion in solution.
EDTA Structure
From the above structure, it is clear that:
It has four -COOH (carboxylic groups), in which two are strongly acidic.
It has two ammonium protons, in which one ionizes at pH of about 6.3 and second ionizes at pH about 11.5. That is why titration is performed in a basic condition
It has six coordination sites (four from acetate oxygen atoms and two from nitrogen atoms.
It makes a stable chelate complex with divalent metals like Mn2+, Pb2+ and Zn2+. That is why the salt of these metals are estimated by EDTA titration.
The most commonly used chelating agent in these titrations is EDTA (Ethylenediaminetetraacetic acid), a hexadentate ligand that forms stable 1:1 complexes with metal ions such as Ca²⁺, Mg²⁺, Zn²⁺, and Fe³⁺.
The principle of complexometric titration is based on the formation of a stable, water-soluble complex between a metal ion and a chelating agent. The endpoint of the titration is typically indicated by a metal ion indicator that changes color when the metal ion is fully complexed.
Key Concepts:
Chelation: The process where a single ligand binds to a metal ion through multiple donor atoms.
End Point Detection: Indicators such as Eriochrome Black T or Murexide are used; they form colored complexes with metal ions, and a sharp colour change indicates the completion of the reaction.
pH Sensitivity: Since complex formation is pH-dependent, buffers are used to maintain the desired pH throughout the titration.
Indicator for EDTA titration
Eriochrome black T, Pyrocatechol and Calmagite
Procedure of Complexometric Titration
Here’s a typical step-by-step procedure:
Materials Required:
Standard EDTA solution
Sample containing metal ions
Suitable metal ion indicator (e.g., Eriochrome Black T)
Buffer solution (e.g., ammonium buffer for pH 10)
Distilled water
Burette, pipette, conical flask
Steps:
Sample Preparation: Accurately measure the sample containing the metal ion and transfer it into a conical flask.
Buffer Addition: Add the appropriate buffer solution to maintain the required pH.
Indicator Addition: Add a few drops of the metal ion indicator.
Titration: Fill the burette with the standard EDTA solution. Slowly titrate the sample while swirling continuously.
Endpoint Detection: Observe the colour change of the solution. For example, in Ca²⁺/Mg²⁺ titration with Eriochrome Black T, the colour changes from wine red to blue at the endpoint.
Calculation: Use the volume of EDTA used to calculate the concentration of the metal ion in the sample.
Applications in the Pharmaceutical Industry
Complexometric titration has a wide range of applications in pharmaceutical analysis, particularly in the quantitative estimation of metal ions. Some key uses include:
1. Determination of Water Hardness:
Used to test purified water and water for injection (WFI), where hardness ions like Ca²⁺ and Mg²⁺ must be controlled.
2. Assay of Pharmaceutical Substances:
Determination of metal-containing drugs like magnesium sulfate, calcium gluconate, or zinc oxide.
3. Quality Control of Raw Materials:
Ensures raw materials used in drug manufacturing meet specifications for metal ion content.
4. Stability Testing:
Used to check if metal ions are contributing to the degradation of drug products during storage.
5. Detection of Trace Metals:
EDTA titration can help detect trace amounts of metal ions that may catalyze oxidation reactions in formulations.
Advantages of Complexometric Titration
High selectivity for specific metal ions
Suitable for both micro and macro analysis
Can be automated for high-throughput testing
Relatively simple and cost-effective
Case Study:
Quantification of Divalent salts like Magnesium oxide and Zinc oxide is performed by EDTA titration.
Conclusion
Complexometric titration remains a cornerstone of pharmaceutical analytical chemistry. Its ability to provide accurate and specific determination of metal ions makes it indispensable in quality control and formulation development. With continued innovations in chelating agents and detection methods, this technique continues to evolve, offering even greater sensitivity and precision.
