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The British Pharmacopoeia method for the analysis of paracetamol involves heating it under reflux with 1 mot dm-3 sulfuric acid. This is a straightforward, acid catalysed, hydrolysis of an amide to an amine and a carboxylic acid. The 4-aminophenol which is formed is then titrated with an oxidising agent, ammonium cerium(lV) sulfate using ferroin as the indicator.

Health, safety and technical notes

  • Read our standard health and safety guidance
  • Wear eye protection.
  • Paracetamol formulations - do not ingest.
  • Sulfuric acid (1 mol dm-3) - corrosive, especially when hot. See CLAPSS Hazcard HC098a
  • Hydrochloric acid (2 mol dm-3) - irritant. See CLAPSS Hazcard HC047a
  • Ferroin solution - hazards unknown. May cause skin irritation. 
  • Ammonium cerium(lV) sulfate - respiratory tract irritant, strong oxidising agent, keep away from flammable material. See CLAPSS Hazcard HC002b


  • Sulfuric acid (1 mol dm-3)
  • Hydrochloric acid (2 mol dm-3)
  • Ammonium cerium(lV) sulfate (0.1 mol dm-3)
  • Paracetamol
  • Water
  • Ferroin solution (0.1 o/o wt or 0.025 mol dm-3)

Apparatus and equipment (per group)

  • Round bottom flask
  • Quick fit reflux apparatus
  • Heating mantle, or Bunsen burner, tripod and gauze
  • Clamps and stand
  • Spatula
  • One 10 cm3 measuring cylinder
  • One 50 cm3 measuring cylinder
  • Burette
  • Two conical flasks
  • Beaker
  • Eye protection


  1. Dissolve 0.3 g of a mixture containing paracetamol n a mixture of water (10 cm3) and 1 mol dm-3 sulfuric acid (30 cm3).
  2. Boil under reflux for 1 hour, cool and dilute with water (100 cm3).
  3. To 20 cm3 of the resulting solution add cold water (40 cm3, 2 mol dm-3 hydrochloric acid (15 cm3) and ferroin solution (0.1 cm’, 0.1 wt% or 0.025 mol dm-3).
  4. Titrate with 0.1 mol dm-3 ammonium cerium(lV) sulfate (VS - volumetric standard) until a yellow colour is produced.
  5. Repeat the operation without the test material being present. The difference between the titration figures represents the amount of ammonium cerium(lV) sulfate required. Each cm3 of 0.1 mol dm-3 ammonium cerium(lV) sulfate is equivalent to 0.007560 g of paracetamol.

This method can be used to analyse the quantity of paracetamol present in many medicines that contain the drug.


How could you prove that the first step in the quantitative analysis of paracetamol involves hydrolysis to 4-aminophenol?


Isolate the material and characterize it, determine the melting point and compare it with the previous one, also tlc, or follow the reaction by running tlc plates using paracetamol and 4-aminophenol as reference spots.