Piracetam

(Ph. Eur. monograph 1733)

C₆H₁₀N₂O₂    142.2    7491-74-9

Nootropic; cortical myoclonus.

Ph Eur

2-(2-Oxopyrrolidin-1-yl)acetamide.

98.0 per cent to 102.0 per cent (dried substance).

White or almost white, powder.

Freely soluble in water, soluble in ethanol (96 per cent).

It shows polymorphism (5.9).

Infrared absorption spectrophotometry (2.2.24).

Comparison  piracetam CRS.

If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in ethanol (96 per cent) R, evaporate to dryness on a water-bath and record new spectra using the residues.

The solution is clear (2.2.1) and colourless (2.2.2, Method II).

Dissolve 2.0 g in water R and dilute to 10 mL with the same solvent.

Liquid chromatography (2.2.29).

Test solution (a)  Dissolve 50.0 mg of the substance to be examined in a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water R and dilute to 100.0 mL with the same mixture of solvents.

Test solution (b)  Dilute 10.0 mL of test solution (a) to 50.0 mL with a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water R.

Reference solution (a)  Dissolve 5 mg of the substance to be examined and 10 µL of 2-pyrrolidone R in a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water R and dilute to 100.0 mL with the same mixture of solvents.

Reference solution (b)  Dilute 1.0 mL of test solution (a) to 100.0 mL with a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water R. Dilute 5.0 mL of this solution to 50.0 mL with a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water R.

Reference solution (c)  Dissolve 50.0 mg of piracetam CRS in a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water R and dilute to 100.0 mL with the same mixture of solvents. Dilute 10.0 mL of this solution to 50.0 mL with a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water R.

• — size: l = 0.25 m, Ø = 4.6 mm,

• — stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 µm).

Mobile phase  Mix 10 volumes of acetonitrile R1 and 90 volumes of a 1.0 g/L solution of dipotassium hydrogen phosphate R; adjust to pH 6.0 with dilute phosphoric acid R.

Flow rate  1.0 mL/min.

Detection  Spectrophotometer at 205 nm.

Injection  20 µL of test solution (a) and reference solutions (a) and (b).

Run time  8 times the retention time of piracetam.

Relative retention  With reference to piracetam (retention time = about 4 min): impurity D = about 0.8; impurity A = about 1.15; impurity B = about 2.8; impurity C = about 6.3.

System suitability  Reference solution (a):

• — resolution: minimum 3.0 between the peaks due to piracetam and impurity A,

• — symmetry factor: maximum 2.0 for the peak due to piracetam.

• — impurities A, B, C, D: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.1 per cent),

• — unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.1 per cent),

• — total: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent),

• — disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).

Maximum 10 ppm.

Dissolve 2.0 g in 20 mL of water R. 12 mL of the solution complies with test A. Prepare the reference solution using lead standard solution (1 ppm Pb) R.

Maximum 1.0 per cent, determined on 1.000 g by drying in an oven at 105 °C.

Maximum 0.1 per cent, determined on 1.0 g.

Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.

Injection  Test solution (b) and reference solution (c).

Calculate the percentage content of C₆H₁₀N₂O₂ from the areas of the peaks and the declared content of piracetam CRS.

Protected from light.

Specified impurities  A, B, C, D.

A. R = H: pyrrolidin-2-one (2-pyrrolidone),

B. R = CH₂-CO-O-CH₃: methyl (2-oxopyrrolidin-1-yl)acetate,

C. R = CH₂-CO-O-C₂H₅: ethyl (2-oxopyrrolidin-1-yl)acetate,

D. R = CH₂-CO₂H: (2-oxopyrrolidin-1-yl)acetic acid.

Ph Eur