Molecular formula. C₁₁H₁₆N₂O₂,HNO₃

Relative molecular mass. 271.3

Graphic formula.

Chemical name. Pilocarpine mononitrate; (3S-cis)-3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-2(3H)-furanone mononitrate; CAS Reg. No. 148-72-1.

Description. Colourless crystals or a white, crystalline powder; odourless.

Solubility. Freely soluble in water; sparingly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R.

Category. Parasympathomimetic; miotic.

Storage. Pilocarpine nitrate should be kept in a tightly closed container, protected from light.

Additional information. Pilocarpine nitrate is very poisonous; it is affected by light. Even in the absence of light, Pilocarpine nitrate is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures.

Requirements

Definition. Pilocarpine nitrate contains not less than 98.5% and not more than 101.0% of C₁₁H₁₆N₂O₂,HNO₃, calculated with reference to the dried substance.

Identity tests

A. Dissolve 10 mg in 5 mL of water, add 2 drops of sulfuric acid (~100 g/l) TS, 1 mL of hydrogen peroxide (~60 g/l) TS, 1 mL of toluene R, and 1 drop of potassium dichromate (100 g/l) TS, and shake well; the toluene layer acquires a violet colour, whereas the aqueous layer remains yellow.

B. To 2 mL of a 0.05 g/mL solution add 2 mL of ferrous sulfate (15 g/l) TS; it yields reaction A described under 2.1 General identification tests as characteristic of nitrates.

C. Melting temperature, about 176°C with decomposition.

Specific optical rotation. Use a 50 mg/mL solution and calculate with reference to the dried substance; = +80° to +83°.

Chlorides. Dissolve 0.7 g in a mixture of 2 mL of nitric acid (~130 g/l) TS and 30 mL of water, and proceed as described under 2.2.1 Limit test for chlorides; the chloride content is not more than 0.35 mg/g.

Clarity and colour of solution. A solution of 1.0 g in 10 mL of water is clear and colourless.

Sulfated ash. Not more than 2.0 mg/g.

Loss on drying. Dry to constant weight at 105°C; it loses not more than 20 mg/g.

pH value. pH of a 5.0 mg/mL solution in water, 3.5 - 4.5.

Related alkaloids. Carry out the test as described under 1.14.1 Chromatography, Thin-layer chromatography, using silica gel R1 as the coating substance and a mixture of 25 volumes of chloroform R, 20 volumes of acetone R, and 0.4 volume of ammonia (~260 g/l) TS as the mobile phase. Apply separately to the plate 5 μl of each of 2 solutions containing (A) 50 mg of the test substance per mL and (B) 1.0 mg of the test substance per mL. After removing the plate from the chromatographic chamber, allow it to dry in air, spray with potassium iodobismuthate TS2, and examine the chromatogram in daylight. Any spot obtained with solution A, other than the principal spot, is not more intense than that obtained with solution B.

Assay. Dissolve about 0.55 g, accurately weighed, in 30 mL of glacial acetic acid R1, and titrate with perchloric acid (0.1 mol/l) VS as described under 2.6 Non-aqueous titration. Method A. Each mL of perchloric acid (0.1 mol/l) VS is equivalent to 27.13 mg of C₁₁H₁₆N₂O₂,HNO₃.

Additional requirement for Pilocarpine nitrate for sterile use

Complies with 3.2 Test for sterility.