Molecular formula. (C₁₆H₁₇N₂O₅S)₂Ca,2H₂O or C₃₂H₃₄CaN₄O₁₀S₂,2H₂O

Relative molecular mass. 774.9

Graphic formula.

Chemical name. Calcium bis[(2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate] dihydrate; calcium bis[[2S-(2α,5α,6β)]3,3-dimethyl-7-oxo-6-[(phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate] dihydrate; CAS Reg. No. 73368-74-8.

Description. A white, fine crystalline powder; odourless or with a faint characteristic odour.

Solubility. Slowly soluble in 120 parts of water.

Category. Antibiotic.

Storage. Phenoxymethylpenicillin calcium should be kept in a well-closed container.

Additional information. Even in the absence of light, Phenoxymethylpenicillin calcium is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures.

Requirements

Definition. Phenoxymethylpenicillin calcium contains not less than 95.0% and not more than 102.0% of (C₁₆H₁₇N₂O₅S)₂Ca, calculated with reference to the anhydrous substance.

Identity tests

• Either tests A and D or tests B, C, and D may be applied.

A. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from phenoxymethylpenicillin calcium RS or with the reference spectrum of phenoxymethylpenicillin calcium.

B. To 2 mg in a test-tube add 1 drop of water followed by 2 mL of sulfuric acid (~1760 g/l) TS and mix; the solution is colourless. Immerse the test-tube for 1 minute in a water-bath; the solution remains colourless.

C. Place 2 mg in a test-tube, add 1 drop of water and 2 mL of formaldehyde/sulfuric acid TS and mix; the solution is red. Immerse the test-tube for 1 minute in a water-bath; a red-brown colour is produced.

D. Ignite a small quantity, dissolve the residue in hydrochloric acid (~70 g/l) TS, and make the solution alkaline by the addition of ammonia (~100 g/l) TS; the solution yields the reactions described under 2.1 General identification tests as characteristic of calcium.

Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A, using about 0.2 g of the substance; not more than 50 mg/g.

pH value. pH of a 5.0 mg/mL solution in carbon-dioxide-free water R, 5.0-7.5.

p -Hydroxyphenoxymethylpenicillin. Dissolve about 0.11 g, accurately weighed, in sufficient sodium hydroxide (0.1 mol/l) VS to produce 100 mL. Measure the absorbance of a 1-cm layer at the maximum at about 306 nm; not more than 0.36 (use preferably 2-cm cells for the measurement and calculate the absorbance of a 1-cm layer).

Ultraviolet absorbance range. Dilute 20 mL of the solution obtained in the test for p-hydroxyphenoxymethylpenicillin to 100 mL with sodium hydroxide (0.1 mol/l) VS. Measure the absorbance of a 1-cm layer at the maximum at about 274 nm; not less than 0.56 and not more than 0.62.

Assay. Dissolve about 50 mg, accurately weighed, in sufficient water to produce 1000 mL. Transfer two 2.0-mL aliquots of this solution into separate stoppered tubes. To one tube add 10.0 mL of imidazole/mercuric chloride TS, mix, stopper the tube, and place it 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 10.0 mL of water and mix (solution B).

Without delay measure the absorbance of a 1-cm layer at the maximum at about 325 nm against a solvent cell containing a mixture of 2.0 mL of water and 10.0 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 (C₁₆H₁₇N₂O₅S)₂Ca in the substance being tested by comparison with phenoxymethylpenicillin potassium RS, similarly and concurrently examined, taking into account that each mg of phenoxymethylpenicillin potassium RS (C₁₆H₁₇KN₂O₅S) is equivalent to 0.951 mg of phenoxymethylpenicillin calcium (C₁₆H₁₇N₂O₅S)₂Ca. In an adequately calibrated spectrophotometer the absorbance of the reference solution should be 0.63 ± 0.03.