Monographs: Pharmaceutical substances: Piperazini citras - Piperazine citrate

Molecular formula. (C4H10N2)3,2C6H8O7 or C24H46N6O14 (anhydrous)

Relative molecular mass. 642.7 (anhydrous)

Graphic formula.

Chemical name. Piperazine 2-hydroxy-1,2,3-propanetricarboxylate (3:2); hexahydro-1,4-diazine citrate (3:2); CAS Reg. No. 144-29-6 (anhydrous).

Description. A fine, white, granular powder; almost odourless.

Solubility. Soluble in 1.5 parts of water; practically insoluble in ethanol (~750 g/l) TS and ether R.

Category. Anthelmintic.

Storage. Piperazine citrate should be kept in a well-closed container, protected from light.

Piperazine citrate contains a variable amount of water of crystallization.

Requirements

Definition. Piperazine citrate contains not less than 98.0% and not more than 101.0% of (C4H10N2)3,2C6H8O7, calculated with reference to the anhydrous substance.

Identity tests

A. Dissolve 0.1 g in 5 mL of water, add 0.5 g of sodium hydrogen carbonate R, 0.5 mL of freshly prepared potassium ferricyanide (50 g/l) TS, and 0.1 mL of mercury R. Shake vigorously for 1 minute, and allow to stand for 20 minutes; a reddish colour slowly develops.

B. A 20 mg/mL solution yields reaction A described under 2.1 General identification tests as characteristic of citrates.

C. Melting temperature, after drying at 105°C, about 185°C.

D. Dissolve 0.2 g in 5 mL of hydrochloric acid (~70 g/l) TS, and add 0.5 g of sodium nitrite R. Cool in ice for 15 minutes, stir if necessary to induce crystallization, filter, wash with 10 mL of ice-water, and dry the precipitate at 105°C; melting temperature, about 158°C (N,N'-dinitrosopiperazine).

Heavy metals. Use 1.0 g for the preparation of the test solution as described under 2.2.3 Limit test for heavy metals, Procedure 1; determine the heavy metals content according to Method A; not more than 20 μg/g.

Sulfated ash. Not more than 1.0 mg/g.

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; the water content is not less than 0.10 g/g and not more than 0.14 g/g.

pH value. pH of a 0.05 g/mL solution, 5.0-6.0.

Primary amines. For the preparation of the test solution dissolve 0.25 g in sufficient water to produce 50 mL. Transfer 0.5 mL of this solution to a test-tube. Separately transfer to a second test-tube 0.5 mL of a solution containing 10 μg/mL of ethylenediamine R to serve as a reference solution. To both tubes add 0.5 mL of ethanol (~750 g/l) TS, 1 mL of diethoxytetrahydrofuran/acetic acid TS, heat on a water-bath at 80°C for 30 minutes, cool in ice, and add 3 mL of 4-dimethylaminobenzaldehyde TS4. Measure the absorbance at about 570 nm, 7-10 minutes after the addition of the last reagent, against a solvent cell containing the reagents prepared in a similar manner. The absorbance of the test solution is not more intense than that of the reference solution.

Assay. Dissolve about 0.20 g, accurately weighed, in 3.5 mL of sulfuric acid (0.5 mol/l) VS and 10 mL of water, add 100 mL of trinitrophenol (7 g/l) TS, heat on a water-bath for 15 minutes, and allow to stand for 1 hour. Filter, wash the residue with successive quantities of trinitrophenol (7 g/l) TS, using 10 mL each time, until the washings are free from sulfates. Finally, wash with dehydrated ethanol R, and dry the residue to constant weight at 105°C. Each g of residue is equivalent to 393.5 mg of (C4H10N2)3,2C6H8O7.

to previous sectionto next section