Method of Analysis for Sodium Propyl Parabean

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1. Description

White crystalline powder, odorless or almost odorless, hygroscopic.

                                                                                                                  

2. Solubility

Freely soluble in water and in ethanol (50%), sparingly soluble in ethanol (95%), practically insoluble in fixed oils and in methylene chloride.

3. Identification

A. Melting Point

Limit: Between 96°C and 99°C

B. The IR absorption spectrum of precipitate is concordant with the propyl paraben reference spectrum or with the spectrum obtained from propyl paraben WRS.

C. By Thin Layer Chromatography

The principal spot in the chromatogram obtained with test solution (b) is similar in position and size to the principal spot in the chromatogram obtained with reference solution (c). (Refer the test for related substances)

D. Reaction of sodium salt

Reaction (A)

Reagent required

15 % w/v solution of potassium carbonate

Potassium antimonate solutionProcedure

Ignite the precipitate obtained in “Identification test B”. Dissolve 0.1 g of ignited substance in 2 ml of water. Add 2 ml of 15 % w/v solution of potassium carbonate and heat to boiling. No precipitate is produced. Add 4 ml of a freshly prepared potassium antimonate solution and heat to boiling. Allow cooling in ice and if necessary scratch the inside of the test-tube with a glass-red a dense white precipitate is formed.

Reaction (B)

Reagent required

1M Acetic Acid

Magnesium Uranyl acetate solution

Procedure

Ignite the precipitate obtained in “Identification test B”. Dissolve 0.1 g of ignited substance in 2 ml of water. Acidity with 1M acetic acid. Add a large excess of Magnesium Uranyl acetate solution mix. A yellow, crystalline precipitate is formed.

E. Color Reaction: An orange to red color is developed

Reagent required

Sodium carbonate solution

Aminopyrazolone solution

Potassium ferricyanide solution

Procedure

Weigh & transfer about 10 mg of the sample in a test tube, add 1 ml of sodium carbonate solution, boil for 30 seconds and cool. Add 5 ml of aminopyrazolone solution and 1 ml of potassium ferricyanide solution and mix. An orange to red color is developed.

4. pH

Limit: Between 9.5 and 10.5

Procedure

Dissolve 0.1 g sample 100 ml of water and measure the pH of solution.

5. Appearance of solution

Clarity of solution

Reagent required

10% w/v solution of hexamine

Hydrazine sulphate AR.

Methanol AR

Sample Solution: Weigh accurately about 10.0 g. of the sample and transfer into a clean and dried 100 ml volumetric flask, dissolve in water and make up to volume to 100 ml with water. (Solution S)

Reference suspension I: Weigh accurately about 1.0 g. of hydrazine sulphate and transfer into a clean and dried 100 ml volumetric flask, dissolve in water and make up to volume to 100 ml with water and allow standing for 4 to 6 hrs. Add 25 ml of this solution to 25 ml of 10% w/v solution of hexamine mix well and allow standing for 24 hrs. Mix well. Dilute 15 ml of above solution to 1000 ml with water. Dilute 5.0 ml of this suspension (after shaking) to 100 ml with water.

Procedure

Into separate matched, flat-bottomed Nessler cylinders, 15 to 25 mm in internal diameter and of colourless, transparent, neutral glass, place sufficient quantity of the sample solution, reference suspension and water, such that the Nessler cylinders are filled to a depth of 40 mm. After five minutes, compare the contents against a black background by viewing in diffused daylight down the vertical axes of the cylinders. The sample solution is more clear or same as compared to the diluent (water) or is less opalescent than reference suspension.

6. Color of solution

Reagent required

Yellow Primary Solution

Red Primary Solution
Blue Primary Solution

1 % w/v Hydrochloric acid

Reference solution BY6: In a clean and dried 100 ml volumetric flask, transfer 24 ml of yellow primary solution, 10 ml of red primary solution and 4 ml of blue primary solution. Make up the volume to 100 ml with 1% w/v of hydrochloric acid. Dilute 5.0 ml of above solution to 100 ml with 1.0% w/v HCl.

Sample solution:  Use solution S

Procedure

Using identical tubes of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm compare a 40-mm layer of the liquid being examined with a 40-mm layer of water or of the reference solution BY6. Examine the columns of the liquid in diffused daylight by viewing down the vertical axes of the tubes against a white background. The appearance of sample solution is same as that of water or the color intensity of sample solution is not greater than that of reference solution BY6.

7. Chloride

Limit: Not more than 330 ppm

Nitric acid AR

0.1M silver nitrate

Chloride standard solution (25 ppm Cl)

Standard solution: Transfer 10 ml of chloride standard solution (25 ppm Cl) into a clean and dried Nessler cylinder, add 5 ml of water.

Sample solution: Dissolve 1.0 g of sample in 20 ml of water; add 0.2 ml of nitric acid and filter. Transfer 15 ml of the filtrate into a clean and dried Nessler cylinder.

Procedure

Add 10 ml of nitric acid to both cylinders and add sufficient water to make volume to 50 ml. Add 1 ml of 0.1 M silver nitrate, mix and allow standing for 5 minutes protected from direct sunlight. Compare the opalescence if any, produced in the sample solution with that produced with standard solution. The sample solution is less opalescent as compare to the standard solution when viewed transversely against a black background.

8. Sulphate

Limit: Not more than 300 ppm

Reagent required

25 % w/v solution of barium chloride

Sulphate standard solution ( 10 ppm SO4)

5M acetic acid

2M hydrochloric acid

Standard preparation: 15 ml of Sulphate standard solution (10 ppm SO₄).

Sample preparation: Pipette out 25 ml of solution S into a clean, dried 50 ml volumetric flask, add 5 ml of water and 10 ml of hydrochloric acid, dilute to 50 ml with water and filter. Dilute 10 ml of the filtrate to 15 ml with water.

Procedure

Into two separate Nessler cylinders take 1.5 of Sulphate Standard solution (10 ppm SO₄), add 1 ml of 25 % w/v solution of barium chloride. Mix allow to stand for 1 minute. Add 15 ml of sample preparation and 15 ml of standard preparation. Add 0.5 ml of 5M acetic acid. Allow to stand for 5 minutes. Compare the opalescence if any, produced in the sample preparation with that produced with standard solution. The opalescence produced with the sample preparation is not more intense than that with standard solution

9. Related substance

By Thin Layer Chromatography

Stationary phase: silica gel 60 F254

Mobile Phase preparation: Mix 1 volume of glacial acetic acid, 30 volumes of water and 70 volumes of methanol.

Test solution (a): Weigh accurately about 100 mg of the sample and transfer it into a 125 ml separating funnel. Add 10 ml of water and then add 2 ml of hydrochloric acid. Extract with 50 ml of ether. Collect the ether extract and evaporate to dryness. Dissolve the residue in 10 ml of acetone.

Test solution (b): Dilute 1 ml of test solution (a) to 10 ml with acetone.

Reference solution (a): Weigh accurately 34.3 mg of 4-hydroxybenzoic acid and transfer it into a 100-ml volumetric flask. Dissolve it in acetone and make up the volume to 100 ml with acetone.

Reference solution (b): Dilute 0.5 ml of the test solution (a) to 100 ml with acetone.

Reference solution (c): Weigh accurately 10 mg of propyl parahydroxybenzoate WRS and transfer it into a 10 ml volumetric flask. Dissolve in acetone and make up the volume to 10 ml with acetone.

Reference solution (d): Weigh accurately 10 mg of ethyl parahydroxybenzoate WRS and transfer it into a 10 ml volumetric flask. Dissolve in 1 ml of test solution (a) and dilute to 10 ml with acetone.

Procedure

Apply separately to the plate 5ml of each solution. Keep the plate into the TLC chamber, previously saturated with the mobile phase and allows the mobile phase to run over the path of 15 cm. Remove the plate from the TLC chamber and allow it to dry in air. Examine in the ultraviolet light at 254 nm. In the chromatogram obtained with the test solution (a): any spot due to 4-hydroxybenzoic acid is not more intense than the spot in the chromatogram obtained with the reference solution (a) (4%); and any spot, apart from the principal spot and the spot due to 4-hydroxybenzoic acid, is not more intense than the spot in the chromatogram obtained with the reference solution (b) (0.5%). The test is not valid unless the chromatogram obtained with the reference solution (d) shows two clearly separated spots.

10. Heavy metals

Limit: Not more than 10 ppm

Reagent required

Strong ammonia

Thioacetamide reagent

Acetate buffer pH 3.5  

Lead standard solution (10 ppm Pb)

25% w/v Magnesium sulfate in 1M sulphuric acid

2M Hydrochloric acid

Phenolphthalein solution

Sample preparation: Weigh accurately and transfer 2.0 g. of the sample in a silica crucible with 4 ml of a 25% w/v solution of magnesium sulfate in 1 M sulphuric acid.  Mix using a glass rod and heat cautiously to dryness on a water bath. Keep the crucible in muffle furnace. Progressively heat to ignition, below 800°C and continue heating until a white or at most grayish residue is produced. Allow to cool, moisten the residue with 0.2 ml of 1M sulfuric acid, evaporate, ignite again and allow cooling. The total period of ignition should not exceed 2 hours.  Dissolve the residue using two 5-ml quantities of 2M hydrochloric acid. Add 0.1 ml of phenolphthalein solution and add strong ammonia drop wise until a pink color is produced.  Cool, add glacial acetic acid until the solution is decolorized and add a further 0.5 ml.  Filter, if necessary and dilute the solution to 20 ml with water.

Standard solution: Take 2 ml of lead standard solution (10 ppm lead) in a silica crucible, add 4 ml of 25% w/v solution of magnesium sulphate in 1 M sulphuric acid and repeat the procedure beginning at the words “Mix using a glass rod………” under sample preparation.

Procedure

Take two clean and dried Nessler cylinders for sample and standard solution. In sample cylinder pipette out 12 ml of sample solution and in standard cylinder pipette out 2 ml of sample solution and 10 ml of standard solution. Add to the both cylinders, 2 ml of acetate buffer pH 3.5, mix and add 1.2 ml of thioacetamide reagent, mix, allow standing for 2 minutes. Any brown color produced in the sample solution is not more intense than that produced in the standard solution.

11. Water

Limit: Not more than 5.0%

Reagent required

Anhydrous methanol AR

KF reagent Pyridine free single solution

Procedure

Take about 40 ml of anhydrous methanol in the titration vessel, neutralize with KF reagent and find out the factor of KF reagent in mg H2O/ 5 ml in triplicate and enter mean value.

Add accurately about 500 mg of the sample to the titration vessel. Allow to titrate with KF reagent to the electrometric end point. Record the percentage of water content obtained by Karl Fischer titrator. Find out water content of sample in triplicate and take mean value.

12. Assay

Limit: Not less than 99.0% and Not more than 102.0% of C₁₀H₁₁NaO₃, calculated with reference to the anhydrous substance.

Reagent required

Glacial acetic acid

0.1M Perchloric acid

Procedure

Weigh accurately about 150 mg. of the sample in a clean, dried titration beaker, add 50 ml of glacial acetic acid and dissolve. Connect the beaker to the Autotitrator and determine the end-point potentiometrically. Perform a blank titration without the sample. 1 ml of 0.1M Perchloric acid is equivalent to 20.22 mg. of C₁₀H₁₁NaO₃.

Calculation:

Net Volume = sample burette reading – blank reading

                                                        V x F x M x 100 x 100                100

% Assay on anhydrous basis = ----------------------------- x --------------------

                                                                   0.1 x W                      (100 - % water)

Where,

V = Consumed volume of 0. 1M Perchloric acid

M = Molarity of 0. 1M Perchloric acid           

F = Factor

W = Weight of sample

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