Description. A white or almost white, crystalline powder.

Category. Antibacterial drug.

Storage. Procaine benzylpenicillin powder for injections should be protected from light and stored at a temperature not exceeding 25 °C.

Labelling. The designation on the container should state the nature of the buffering agent. Expiry date.

Additional information. Strength in the current WHO Model list of essential medicines: 1 g and 3 g.

Requirements

The powder for injections and the reconstituted preparation for injections comply with the monograph for "Parenteral preparations".

Definition. Procaine benzylpenicillin powder for injections is a sterile powder of procaine benzylpenicillin. Procaine benzylpenicillin powder for injections usually contains a suitable buffering agent. The powder is sterilized by a suitable method (see 5.8 Methods of sterilization). The reconstituted preparation is a suspension.

The container of Procaine benzylpenicillin powder for injections contains not less than 90.0% and not more than 110.0% of the amount of total penicillins calculated as C₁₆H₁₈N₂O₄S,C₁₃H₂₀N₂O₂ and not less than 36.0% and not more than 44.0% of C₁₃H₂₀N₂O₂ both stated on the label.

Identity tests

A. To a quantity of the powder for injections equivalent to 2 mg of Procaine benzylpenicillin in a test-tube add 0.05 mL of water followed by 2 mL of sulfuric acid (~1760 g/l) TS and mix; the solution is almost colourless. Immerse the test-tube for 1 minute in a water-bath; the solution remains almost colourless. Place the same quantity of the powder for injections in a second test-tube, add 1 drop of water and 2 mL of formaldehyde/sulfuric acid TS, and mix; the solution is almost colourless and after a few minutes the colour changes to yellow-brown. Immerse the test-tube for 1 minute in a water-bath; a reddish brown colour is produced.

B. Dissolve a quantity of the powder for injections equivalent to 10 mg of Procaine benzylpenicillin in 10 mL of water and add 0.5 mL of neutral red/ethanol TS. Add sufficient sodium hydroxide (0.01 mol/l) VS to give a permanent orange colour and then add 1 mL of penicillinase TS; the colour changes rapidly to red.

C. A quantity of the powder for injections equivalent to 50 mg of Procaine benzylpenicillin yields the reaction described for the identification of primary aromatic amines under 2.1 General identification tests, producing a bright, orange-red precipitate.

Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A, using a quantity of the powder for injections equivalent to 0.5 g of Procaine benzylpenicillin; the water content is not less than 28 mg/g and not more than 42 mg/g.

Assays

Mix the contents of 10 containers and carry out the assays as described.

Total penicillins. Suspend a quantity of the powder for injections equivalent to about 0.045 g of Procaine benzylpenicillin, accurately weighed, in sufficient water to produce 1000ml. Transfer two 2-mL aliquots of this suspension into separate stoppered tubes. To one tube add 10 mL of imidazole/mercuric chloride TS, mix, stopper the tube, and place in a water-bath at 60 °C for exactly 25 minutes. Cool the tube rapidly to 20 °C (solution A). To the second tube add 10 mL of water and mix (solution B).

Without delay measure the absorbance of a 1-cm layer at the maximum at about 314 nm against a solvent cell containing a mixture of 2 mL of water and 10 mL of imidazole/mercuric chloride TS for solution A and water for solution B.

From the difference between the absorbance of solution A and that of solution B, calculate the amount of C₁₆H₁₈N₂O₄S,C₁₃H₂₀N₂O₂ in the substance being examined by comparison with 0.050 g of benzylpenicillin sodium RS, taking into account that each mg of benzylpenicillin sodium RS (C₁₆H₁₇N₂NaO₄S) is equivalent to 1.601 mg of C₁₆H₁₈N₂O₄S,C₁₃H₂₀N₂O₂. In an adequately calibrated spectrophotometer the absorbance of the reference solution should be 0.62 ± 0.03.

Procaine. Suspend a quantity of the powder for injections equivalent to about 0.5 g of Procaine benzylpenicillin, accurately weighed, in 10 mL of water, add 5 mL of sodium carbonate (75 g/l) TS, and extract with four successive quantities, each of 25 mL, of chloroform R, filter the chloroform extracts, and evaporate to a small volume on a water-bath. Add 20 mL of hydrochloric acid (0.1 mol/l) VS and distil off the remaining chloroform. Cool, add 0.25 mL of methyl red/ethanol TS, and back-titrate with sodium hydroxide (0.1 mol/l) VS.

Each mL of hydrochloric acid (0.1 mol/l) VS is equivalent to 23.63 mg of C₁₃H₂₀N₂O₂.

Bacterial endotoxins. Carry out the test as described under 3.4 Test for bacterial endotoxins; contains not more than 0.01 IU of endotoxin RS per mg of benzylpenicillin.