1. Description
White or yellowish-white powder or flakes, hygroscopic.2. Solubility
Freely soluble in water, in alcohol and in methylene chloride.3. Identification
A. The IR absorption spectrum of the sample should be concordant with the reference spectrum obtained with the Copovidone WRS.B. Color test
Reagent required0.1N Iodine solution.
Starch test solution.
Procedure: Dissolve 10gm of the sample in water and dilute to 100ml with the same solvent. Add the substance to be examined to the water in small portions with constant stirring (Solution S). To 1 ml of solution S add 5 ml of water and 0.2 ml of 0.05M iodine. A red color appears.
C. Color Test
Procedure: Dissolve 0.7 gm of hydroxylamine hydrochloride in 10 ml of methanol, add 20 ml of a 40 g/l solution of sodium hydroxide and filter if necessary. To 5 ml of the solution add 0.1 gm of the sample and boil for 2 min. Transfer 50 µl to a filter paper and add 0.1 ml of a mixture of equal volumes of ferric chloride solution and hydrochloric acid. A violet color appears.4. Appearance of the solution
Limit: Solution S is not more opalescent than reference suspension III and not more intensely colored than reference solution B5, R5 or BY5Clarity of the solution
Test Preparation: Solution SStandard of Opalescent: Dissolve 1.0 g of hydrazine sulfate in sufficient water to produce 100.0 ml and allow standing for 4 to 6 hours. Add 25.0 ml of this solution to a solution containing 2.5 g of hexamine in 25.0 ml of water mix well and allow standing for 24 hours. Dilute 15.0 ml of the suspension to 1000.0 ml with water.
Reference Solution III: Take 30 ml of the standard of opalescent in 100 ml volumetric flask and make up the volume to 100 ml.
Take both the solution in a Nessler cylinder and view under the white background. Opalescent of the test solution is not more than standard solution.
Color of the solution
Test Preparation: Solution SStandard Solution: Prepare solution B by mixing 30ml of yellow primary standard solution, 30ml of red primary solution, 24 ml of blue primary solution and 16 ml of 1% W/V HCl. (Solution B)
Solution B5: Take 12.5 ml of solution B in the 100ml volumetric flask then make up the volume to 100 ml with 1.0% w/v of HCl.
Compare the solution B5 and Test preparation under the white background. The test preparation is not more intensely colored than the standard solution
5. Aldehyde
Limit: NMT 500 ppmProcedure: Test solution: Dissolve 1.0 gm of the substance to be examined in phosphate buffer solution pH 9.0 and dilute to 100.0 ml with the same solvent. Stopper the flask and heat at 60°C for 1 h. Allow cooling.
Reference solution: Dissolve 0.140 g of acetaldehyde ammonia trimer trihydrate in water and dilute to 200.0 ml with the same solvent. Dilute 1.0 ml of this solution to 100.0 ml with phosphate buffer solution pH 9.0.
Into 3 identical spectrophotometric cells with a path length of 1 cm, introduce separately 0.5ml of the test solution, 0.5ml of the reference solution and 0.5ml of water (blank). To each cell, add 2.5ml of phosphate buffer solution pH 9.0 and 0.2ml of nicotinamide-adenine dinucleotide solution. Mix and stopper tightly. Allow to stand at 22°C ±2°C for 2-3 min and measure the absorbance of each solution at 340 nm, using water as the compensation liquid. To each cell, add 0.05 ml of aldehyde dehydrogenase solution, mix and stopper tightly. Allow standing at 22°C ±2°C for 5 min. Measure the absorbance of each solution at 340 nm using water as compensation liquid. Determine the content of aldehydes using the expression:
(At2 – At1) - (Ab2 – Ab1) 100000 x C
= ----------------------------------- X ----------------
(As2 – As1) - (Ab2 – Ab1) m
At1 = absorbance of the test solution before the addition of aldehyde dehydrogenase,
At2 = absorbance of the test solution after the addition of aldehyde dehydrogenase,
As1 = absorbance of the reference solution before the addition of aldehyde dehydrogenase,
As2 = absorbance of the reference solution after the addition of aldehyde dehydrogenase,
Ab1 = absorbance of the blank before the addition of aldehyde dehydrogenase,
Ab2 = absorbance of the blank after the addition of aldehyde dehydrogenase,
m = mass of povidone, in grams, calculated with reference to the dried substance,
C = concentration (mg/ml), of acetaldehyde in the reference solution, calculated from the weight of the acetaldehyde ammonia trimer trihydrate with the factor 0.72.
6. Peroxide
Limit: Not more than 400 ppmProcedure: Dilute 10 ml of solution S to 25 ml with water. Add 2 ml of titanium trichloride-sulphuric acid reagent and allow to stand for 30 min. The absorbance of the solution, measured at 405 nm using a mixture of 25 ml of a 40 g/l solution of the substance to be examined and 2 ml of a 13 percent V/V solution of sulphuric acid as the compensation liquid, is not greater than 0.35.
7. Hydrazine
Limit: Any spot corresponding to salicylaldehyde azine in the chromatogram obtained with the test solution is not more intense than the spot in the chromatogram obtained with the reference solution (1 ppm).Procedure: Plate: TLC silica gel silanised H plate.
Mobile phase: water, methanol (20:80 V/V).
Application: 10 µl.
Development: over a path of 15 cm.
Drying: in air.
Detection: examine in ultraviolet light at 365 nm.
Test solution: To 25 ml of solution S add 0.5 ml of a 50 g/l solution of salicylaldehyde in methanol, mix and heat in a water-bath at 60°C for 15 min. Allow to cool, add 2.0 ml of xylene, shake for 2 min and centrifuge. Use the clear supernatant layer.
Reference solution: Dissolve 9 mg of salicylaldehyde azine in xylene and dilute to 100 ml with the same solvent. Dilute 1 ml of this solution to 10 ml with xylene.
Inject 10µl of the test and standard preparation on the plate and develop over a path of 15 cm using mobile phase. Then dry the plate in the air and examine under ultraviolet light at 365 nm.
Any spot corresponding to salicylaldehyde azine in the chromatogram obtained with the test solution is not more intense than the spot in the chromatogram obtained with the reference solution (1 ppm).
8. Monomer
Limit: Not more than 0.1%Procedure: Dissolve 10 gm of the sample in 30ml of methanol and add slowly 20ml of iodine bromide solution. Allow standing for 30 min protected from light with repeated shaking. Add 10 ml of a 100g/l solution of potassium iodide and titrate with 0.1M sodium thiosulphate until a yellow color is obtained. Continue titration dropwise until the solution becomes colorless. Carry out a blank titration. Not more than 1.8ml of 0.1M sodium thiosulphate is used.
9. Impurity A by HPLC
Limit: Not more than 0.5%Procedure: Test solution: Dissolve 100 mg of the substance to be examined in water and dilute to 50.0 ml with the same solvent.
Reference solution: Dissolve 100 mg of 2-pyrrolidone in water and dilute to 100 ml with the same solvent. Dilute 1.0 ml to 100.0 ml with water.
Mobile phase: Water, adjusted to pH 2.4 with phosphoric acid.
Pre Column:
Size: l = 0.025 m, Ø = 4 mm
Stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 µm).
Chromatographic System
| |
Column
Detector
Flow rate
Injection volume
Run time
|
0.25m X 4.0 mm X 5 µm
At 205 nm
1.0ml/ minute
10ml
|
Injection: 10 µl. When impurity A has left the precolumn (after about 1.2 min) switch the flow directly from the pump to the analytical column. Before the next chromatogram is run, wash the precolumn by the reversed flow.
Limits:
Impurity A: not more than the area of the principal peak obtained with the reference solution (0.5 percent).
10 Loss on Drying
Limit: Not more than 5.0 %Procedure: Weigh 0.5g of the sample in a dried pre-weighed LOD Bottle. Cover the stopper and gently shake to distribute material to not more than 10 MM height. Place the LOD Bottle in the oven and remove the cover and leave it also inside the oven. Dry the sample at 105°C 3 hours on opening the chamber, immediately close the LOD Bottle, transfer it to desiccators and bring it to room temperature. Weigh up to constant weight.
Calculation
W2 – W3
% LOD = ------------------- X 100
W2 – W1
Where,
W1 = Weight of empty clean and dried LOD Bottle.
W2 = Weight of LOD Bottle + sample.
W3 = Weight of LOD Bottle + sample. (After drying)
11. Sulphated Ash
Limit: Not more than 0.1 %Reagent required
Sulphuric acid
Procedure: Heat a silica crucible to redness for 10 min., allow to cool in a desiccator and weigh. Place about 2 g of the accurately weighed substance being examined in the silica crucible and ignite at about 800o, cool, weigh and again, ignite for 15 min.and repeat this procedure until two successive weighing does not differ by more than 0.5 mg.
Calculation
W3– W1
% Residue on ignition = -----------------x 100
W2 – W1
Where:
W1 = Weight of empty platinum crucible.
W2 = Weight of crucible + sample.
W3 = Weight of crucible + residue. (After ignition)
12. Heavy Metals
Limit: Not more than 20 ppmReagent required
Lead standard solution (2ppm.Pb.)
Acetate Buffer pH 3.5
Thioacetamide Reagent
Standard solution: Pipette 10 ml of lead standard solution (2 ppm Pb) and transfer to 50 ml Nessler cylinder. To this add 2 ml of acetate buffer pH 3.5, mix, add to 1.2 ml of thioacetamide reagent, mix immediately and allow standing for 2 minutes.
Sample solution: To 12 ml of the solution S add 2 ml of acetate buffer pH 3.5, mix, add to 1.2 ml of thioacetamide reagent, mix immediately and allow standing for 2 minutes.
Procedure: Each of the cylinders containing the standard solution and sample solution views downwards over a white surface. The brown color produced with the sample preparation is not more intense than that of the standard preparation.
13. Viscosity Expressed as K-Value
Limit: 90-110% of the labeled amountProcedure: Dilute 5.0 ml of solution S to 50.0 ml with water. Allow to stand for 1 h and determine the viscosity of the solution at 25°C ±0.1°C using glass suspended level viscometer No. 1 with a minimum flow time of 100 s. Calculate the K-value from the expression:
Where,
c = percentage concentration (g/100 ml) of the substance to be examined, calculated with reference to the dried substance,
h = viscosity of the solution relative to that of water.
14. Assay: Ethenyl Acetate
Limit: It contains 35.3% to 42.00 of Ethenyl acetate on the dried basis.Procedure: Introduce 2 gm (m) of the sample into a 250-ml borosilicate glass flask fitted with a reflux condenser. Add 25.0 ml of 0.5M alcoholic potassium hydroxide and a few glass beads. Attach the condenser and heat under a reflux condenser for 30 minutes, unless otherwise prescribed. Add 1 ml of phenolphthalein solution and titrate immediately (while still hot) with 0.5M hydrochloric acid VS (n1 ml of 0.5M hydrochloric acid). Carry out a blank test under the same conditions (n2 ml of 0.5M hydrochloric acid).
Multiply the result obtained by 0.1534 to obtain the percentage content of the ethenyl acetate component.
15. Assay: Nitrogen content
Limit: Not less than 7.0 % and not more than 8.0 % of nitrogen, calculated on the anhydrous basis.Reagent required
Dipotassium sulfate
Cupric sulfate
10M Sodium hydroxide
Methyl red-methylene blue TS
0.01M Hydrochloric acid
Procedure: Using 30.0 mg of the sample and 1 g of a mixture of 3 parts of copper sulfate and 997 parts of dipotassium sulfate, heating until a clear, light green solution is obtained and then for a further 45 min. Cool, dissolve the residue by cautiously adding 25 ml of water, cool again and connect the flask to a steam-distillation apparatus. Add 30 ml of 10M sodium hydroxide and distill immediately by passing steam through the mixture. Collect about 40 ml of the distillate in a mixture of 20 ml of 0.01M hydrochloric acid VS and sufficient water to cover the tip of the condenser, taking precautions to prevent water from the outer surface of the condenser from reaching the receiver. Towards the end of the distillation lower the receiver so that the top of the condenser is above the surface of the acid. Titrate the excess of acid with 0.01M sodium hydroxide VS using methyl red mixed solution as indicator. Repeat the operation using 50 mg of D-glucose in place of the substance being examined. The difference between the titrations represents the ammonia liberated by the substance being examined. Each ml of 0.01M hydrochloric acid VS is equivalent to 0.1401 mg of N.
Calculations
Net B.R. = Blank B.R. – Sample B.R.
Where,
B.R. = burette reading.
Net B.R. x F x N x 100
% Content of Nitrogen “as is” = ----------------------------------
0.01x W
Where,
W= Weight of the sample (in mg)
N= Normality of HCl
F= Factor
% Content “as is” x 100
% Content of Nitrogen “On Dried” basis = ---------------------------------
(100 – %Water)
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