भारतीय भेषज संहिता आयोग
Zaleplon
C17H15N5O Mol. Wt. 305.3
Zaleplon is acetamide,N-[3-(cyanopyrazolo[1,5-a]pyrimidin 7-yl)phenyl]-N-ethyl; 3’-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)-N-ethylacetanilide.
Zaleploncontains not less than 98.0 per cent and not more than 102.0 per cent of C17H15N5O, calculated on the anhydrous basis.
Category.Hypnotic; sedative.
Dose.Orally, 10 mg orally.
Description.A white to off-white powder.
Identification
- Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained withzaleplon RSor with the reference spectrum of zaleplon.
- In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution (b).
Tests
Related substances.Determine by liquid chromatography (2.4.14).
Solvent mixture.25 volumes of acetonitrile and 75 volumes of water.
Test solution. Dissolve 50 mg of the substance under examination in 100.0 ml of the solvent mixture.
Reference solution (a). A 0.05 per cent w/v solution of zaleplon RS and 0.00005 per cent w/v solution each of zaleplon related compound A RS, zaleplon related compound B RS and zaleplon related compound C RS (7-[3-(N-ethylacetamido) phenyl] pyrazolo[1,5-α] pyrimidine-3-carboxamide) in solvent mixture.
Reference solution (b).A 0.00005 per cent w/v solution of zaleplon RS in solvent mixture.
Chromatographic system
– a stainless steel column 15 cm x 4.6 mm, packed with octylsilane bonded to porous silica (5 µm),
– mobile phase: A. a solution of 1.4 g of monobasic potassium phosphate in 1000 ml of water and adjust the pH to 3.0 with ortho phosphoric acid,
- acetonitrile,
– a gradient programme using the conditions given below,
– flow rate: 1.5 ml per minute,
– spectrophotometer set at 225 nm,
– injection volume: 10 µl.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
0 80 20
15 60 40
25 45 55
26 80 20
35 80 20
Name Relative Correction
retention time factor
Cyanopyrazolamine1 0.15 2.0
Zaleplonrelated compound A 0.54 2.7
Zaleplonrelated compound C2 0.57 1.25
Desethylzaleplon2,3 0.70 0.90
Zaleplon1.0 ---
Zaleplonrelated compound B1.11 1.53
Zaleplonoxopropenylanalog2,4 1.59 1.96
UnknownImpurity--- 1.0
13-aminopyrazole-4-carbonitrile,
2processimpurity ; may not befound in all manufacturingprocess,
3N-[3-(3-cyanopyrazolo[1,5-α] pyrimidin-7-yl) phenyl] acetamide,
4 (E) –N- [3-(3-cyano-6-{3-[3-(N-ethylacetamido) phenyl] -3- oxoprop-1-en-1-yl} pyrazolo[1,5-α] pyrimidin-7-yl) phenyl ] –N-ethylacetamide.
Inject the reference solution (a).The test is not valid unless the resolution between zaleplon related compound A and zaleplon related compound C is not less than 1.2, zaleplon and zaleplon related compound B is not less than 2.0 per cent.
Inject the reference solution (b). The test is not valid unless the relative standard deviation for replicate injections is not more than 5.0 per cent.
Inject the reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of cyanopyrazolamine, zaleplon related compound A and zaleplon related compound B peak is not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.15 per cent). In the chromatogram obtained with the test solution, the area of zaleplon related compound C, desethylzaleplon, zaleplonoxopropenylanalog and any other single impurity peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.1 per cent). The sum of the areas of all the peaks is not more than 5.0 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent).
Water (2.3.43). Not more than 2.0 per cent.
Heavy metals (2.3.13). 1.0 g complies with the limit test for heavy metals, Method B (20 ppm).
Sulphated ash (2.3.18). Not more than 0.2 per cent.
Assay. Determine by liquid chromatography (2.4.14).
Solvent mixture.Equal volumes of acetonitrile and of water.
Test solution. Dissolve 10 mg of the substance under examination in 100.0 ml of the solvent mixture. Further dilute 5.0 ml of the solution to 10.0 ml with the solvent mixture.
Reference solution (a). A 0.05 per cent w/v solution of zaleplon RS and 0.00005 per cent w/v solution each of zaleplon related compound A RS[(E)-N-{3-[3-(dimethylamino) acryloyl]phenyl}-N-ethylacetamide] and zaleplon related compound BRS( N-[3-(3-cyanopyrazolo[1,5-α]pyrimidin-5-yl)phenyl-N-ethylacetamide) in solvent mixture.
Reference solution (b).A 0.005 per cent w/v solution of zaleplon RS in solvent mixture.
Chromatographic system
– a stainless steel column 10 cm x 4.0 mm, packed with octadecylsilane bonded to porous silica (3 µm),
– mobile phase: a mixture of 180 volumes of a buffer solution prepared by dissolving 0.3 g of ammonium formate in 1000 ml of water, adjusting the pH to 4.0 with formic acid,
– flow rate:1ml per minute,
– spectrophotometer set at 245 nm,
– injection volume: 10 µl.
Name Relative
retention time
Zaleplon 1.0
zaleplon related compound B 1.2
Inject the reference solution (a).The test is not valid unless the resolution between zaleplon and zaleplon related compound B is not less than 2.0.
Inject the reference solution (b). The test is not valid unless the tailing factor is not more than 1.5 and the relative standard deviation for replicate injections is not more than 1.0 per cent.
Inject the reference solution (b) and the test solution.
Calculate the content of C17H15N5O.
Storage. Store protected from light and moisture.
