Assay of Metronidazole
BP607P Medicinal Chemistry III Practical : I Preparation of drugs Sulphanilamide * 7-Hydroxy, 4-methyl coumarin * Chlorobutanol * Triphenyl imidazole * Tolbutamide * Hexamine II Assay of drugs Isonicotinic acid hydrazide * Chloroquine * Metronidazole * Dapsone * Chlorpheniramine maleate * Benzyl penicillin III Microwave irradiation technique Synthesis of Phenytoin by Microwave * Synthesis of Aspirin by Microwave IV Drawing structures and reactions using chem draw®
Aim:
To determine the percentage purity of a given sample of Metronidazole tablet
Principle:
Substances with very weak acid or basic properties do not give a sharp endpoint in an aqueous solution and can be titrated with non-aqueous solvents.
Non-aqueous titration is based on the Bronsted-Lowry theory According to this theory an acid is a proton donor, i.e. a substance which tends to dissociate to yield a proton, and a base is a proton acceptor, i.e. a substance which tends to combine with a proton. When an acid HB dissociates it yields a proton together with the conjugate base B of the acid.
Metronidazole is a weak base and it is assayed by non-aqueous titration. When a weakly basic drug is dissolved in an acidic solvent with titration of perchloric acid, the basic property of the mineral is enhanced.
If a strong acid like perchloric acid is added to acetic acid, the acetic acid behaves as a base and combines with the proton donated by perchloric acid to form an onium ion which acts as a strong acid, the onium ion has readily donated the proton to the base.
The indicator used in this titration is crystal violet. The use of acetic anhydride in this solution, it combines with the water molecule to form acetic acid.
Reaction:
Procedure:
Preparation of Perchloric acid 0.1M
Mixed 8.5 ml of Perchloric acid in 900 ml of glacial acetic acid shake vigorously and continuous stirring. Then added 30 ml acetic anhydride and make up the volume to 1 litre with glacial acetic acid and allowed to stand for 24 hours before use. The acetic anhydride reacts with the water in perchloric acid and some traces in glacial acetic acid thereby making the resulting mixture practically anhydrous.
Standardisation of 0.1 N Perchloric acid
About 0.5g of Potassium hydrogen phthalate were weighed accurately and transferred in a 100 ml conical flask, previously dried at 120oC for 2 hours. 50ml of glacial acetic acid was added, and warmed if necessary, to dissolve the salt completely. Cooled and titrated with 0.1M perchloric acid using crystal violet 0.1ml (2 drops) as an indicator. The endpoint is colour changes from violet to emerald green.
Each ml of 0.1M Perchloric acid = 0.02042g of Potassium Hydrogen Phthalate
Assay of metronidazole:
About 3.0g of metronidazole sample was weighed accurately and transferred into a 250ml conical flask, 50ml of Glacial acetic acid was added, and warmed gently. Cooled and titrated with 0.1M perchloric acid using α-Naphthol benzene as an indicator. The endpoint is colour changes from Blue to Blue-green.
Each ml of 0.1M perchloric acid = 0.02042g of Potassium hydrogen Phthalate.
Report:
The Molarity of 0.1M Perchloric acid=
The Percentage purity of given metronidazole was found to be=
Additional information
Aspirin (acetylsalicylic acid): Aspirin is an acid and can be assayed by titration with a base, such as sodium hydroxide (NaOH), to determine its acid content.
Antacids: Antacid medications, such as Tums (calcium carbonate) or Mylanta (aluminum hydroxide and magnesium hydroxide), are alkaline substances used to neutralize excess stomach acid. Their acid-neutralizing capacity can be assessed by titration with an acid solution, such as hydrochloric acid (HCl).
Vitamin C (ascorbic acid): Vitamin C is an acid and can be analyzed by titration with a base solution, such as sodium hydroxide (NaOH), to determine its acid content.
Ibuprofen: Although not typically assayed by acid-base titration, ibuprofen is a weak acid, and its acid dissociation constant (pKa) can be determined using acid-base titration methods.
Phenolphthalein: Phenolphthalein is a commonly used indicator in both aqueous and non-aqueous titrations. It is often used in non-aqueous solvents like alcohol or acetic acid. Phenolphthalein changes color in the pH range of approximately 8.2 to 10, making it suitable for acid-base titrations.
Bromothymol Blue: Bromothymol Blue is another indicator that can be used in non-aqueous solvents. It has a color change range of pH 6.0 to 7.6 and is suitable for acid-base titrations carried out in non-aqueous solvents.
Thymol Blue: Thymol Blue is an indicator that changes color in the pH range of approximately 8.0 to 9.6. It can be used in non-aqueous titrations involving weak acids or bases.
Methyl Orange: Methyl Orange is an indicator commonly used in acid-base titrations in non-aqueous solvents. It changes color in the pH range of approximately 3.1 to 4.4.
In pharmacy, an assay refers to a quantitative analysis or measurement of the active pharmaceutical ingredient (API) or drug content in a pharmaceutical formulation. It is a critical process used to determine the purity, potency, and quality of a drug product.
The assay provides information about the concentration or amount of the active ingredient present in a drug formulation, ensuring that it meets the required standards and specifications. Assay methods are developed and validated to ensure accuracy, precision, specificity, and reproducibility.
The assay can be performed using various analytical techniques, including spectrophotometry, chromatography (such as high-performance liquid chromatography or gas chromatography), titration, gravimetry, and other instrumental methods. These methods involve the measurement of specific physical or chemical properties of the drug substance or drug product.
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