Zaleplon Capsules

Zaleplon Capsules contains not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of  zaleplon, C17H15N₅O, calculated on the anhydrous basis.

Usual strengths.5mg;10 mg.

Identification

1. 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.
2. When examined in the range 200-400 nm, a 0.01 per cent w/v solution in 1 volumeacetonitrileand 4 volumes water shows an absorption maxima at the same wave length as that the of reference solution.

Tests

Dissolution (2.5.2).

1. Apparatus No. 1 (Use sinkers, if required),

Medium. 900 ml of water,

Speed and time.75 rpm and 20 minutes.

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography (2.4.14).

Test solution. Dilute the filtrate if necessary with the dissolution medium.

Reference solution. Dissolve a quantity of zaleplon RS in sufficient methanol and dilute with the dissolution medium to obtain a solution having a known concentration similar to the expected concentration of the test solution.

Chromatographic system

     –   a stainless steel column 5.0 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (3 µm),

    –    column temperature: 35°,

     –   mobile phase: a mixture of 67 volumes of  a buffer solution prepared by dissolving 0.77 g ammonium acetate in 1000 ml of water and 33 volumes of methanol,

     –   flow rate: 2 ml per minute,

     –   spectrophotometer set at 230 nm,

     –   injection volume: 50 µl.

Inject the reference solution. The test is not valid unless the column efficiency is not less than 2000 theoretical plates and the tailing factor is not more than 1.5 and the relative standard deviation for replicate injections is not more than 2.0 per cent.

Inject the reference solution and the test solution.   

Calculate the content of C17H15N₅O in the medium.

1. Not less than 85 per cent of the stated amount of C17H15N₅O.

Related substances.Determine by liquid chromatography (2.4.14).

Use solvent mixture, test solution and chromatographic system as described under Assay.

Reference solution (a).A 0.05 per cent w/v solution of zaleplon RS in the solvent mixture.

Reference solution(b). A 0.00005 per cent w/v solution of zaleplon related compound BRS inreference solution (a).

Reference solution(c). Dilute 1.0 ml of reference solution (a) in 100.0 ml with the solvent mixture, further dilute 1.0 ml of this solution to 100.0 ml with the same solvent.

Reference solution(d). Dilute 10.0 ml of reference solution (a) in 50.0 ml with the solvent mixture.

Name                                                                               Relative      

                                                    retention time              

Cyanopyrazolamine1*                              0.16                       

Zaleplonrelated compound A2*                                                               0.76     

Zaleplon1.0                                         

Zaleplonrelated compound B3*                            1.05   

UnknownImpurity                                                          ---                      

13-aminopyrazole-4-carbonitrile,

2(E)-N-{3-[3-(dimethylamono)acryloyl]phenyl}-N-ethylacetamide,

3N-[3-(3-cyanopyrazolo[1,5-α]pyrimidin-5-yl)phenyl-N-ethylacetamide,

* included for peak identification only.

Inject reference solution (c). The test is not valid unless the signal–to–noise ratio of  the principal peak is not less than 10.0. 

Inject the reference solution (b).The test is not valid unless the resolution between zaleplon and zaleplon related compound B is not less than 1.5, the tailing factor for zaleplon is not more than 1.5 and the relative standard deviation for the replicate injections is not more than 2.0 per cent.

Inject the reference solution (d) and the test solution. In the chromatogram obtained with the test solution, the area of  any other single impurity peak is not more than 0.002 times the area of the principal peak in the chromatogram obtained with reference solution (d) (0.2 per cent). The sum of the areas of all the peaks is not more than 0.01 times the area of the principal peak in the chromatogram obtained with reference solution (d) (1.0 per cent).

Uniformity of content.Complies with the test stated under Capsules.

Determine by liquid chromatography (2.4.14), using the chromatographic system, solvent mixture and reference solution as described in the Assay.

Test solution. Transfer one capsule in 50.0 ml volumetric flask, disperse in minimum quantity of water and add sufficient quantity of solvent mixture, shake for 10 minutes, filter. Dilute to volume with solvent mixture. Dilute if, necessary with the solvent mixture.

Calculate the content of C17H15N₅O in the capsule.

Other tests. Comply with the tests stated under Capsules.

Assay. Determine by liquid chromatography (2.4.14).

Solvent mixture.10 volumes of acetonitrile and 40 volumes of water.

Test solution. Place 5 intact capsules in to a 250- ml volumetric flask, disperse in 50 ml of the solvent mixture, with the aid of ultrasound for 10 minutes and dilute to volume with the same solvent. Dilute if, necessary with the solvent mixture.

Reference solution.A 0.01 per cent w/v solution of zaleplon RS in solvent mixture

Chromatographic system

     –   a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),

–   mobile phase:     A. a mixture of 0.3 g of ammonium formate in 1000 ml of water,

1.  acetonitrile,

     –   a gradient programme using the conditions given below,

–    flow rate:1.4 ml per minute,

     –   spectrophotometer set at 240 nm,

     –   injection volume: 15 µl.

Time   Mobile phase A Mobile phase B

           (in min.)          (per cent v/v)               (per cent v/v)

                  0                          95                                   5

                30                         50                                  50

                31                         95                                   5

Inject the reference solution. 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 2.0 per cent.

Inject the reference solution and the test solution.   

Calculate the content of C17H15N₅O.

Storage. Store protected from light and at controlled room temperature.