Method of Analysis for Maleic Acid : Pharmaguideline
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  • Jun 22, 2008

    Method of Analysis for Maleic Acid

    Procedure for analysis of Maleic Acid in pharmaceutical quality control laboratory.

    1. Description

    A white, crystalline powder.

    2. Solubility

    Freely soluble in water and in alcohol, sparingly soluble in ether.

    3. Identification

    Solution S: Dissolve 5.0 g in water and dilute to 50 ml with the same solvent.
    A. Dilute 5 ml of solution S to 10 ml with water. The pH of the dilution is less than 2.
    B. Examine the chromatograms obtained in the test for fumaric acid. 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 (a).

    C. Dissolve 0.1 g in 10 ml of water (solution a). To 0.3 ml of solution (a) add a solution of 10 mg of resorcinol in 3 ml of sulphuric acid. Heat on a water-bath for 15 min; no color develops. To 3 ml of solution (a) add 1 ml of bromine water. Heat on a water-bath to remove the bromine (15 min), heat to boil and cool. To 0.2 ml of this solution add a solution of 10 mg of resorcinol in 3 ml of sulphuric acid. Heat on a water-bath for 15 min. A violet-pink color develops.

    4. Appearance of the solution

    Limit: The solution is clear and not more intensely colored than reference solution Y7
    Procedure: Test Solution: Solution S
    Reference Solution Y7: Prepare Y solution by mixing 24 ml of yellow primary standard solution, 6 ml of red primary solution, 70 ml of 1% w/v of Hydrochloric acid. Now take 2.5 ml of this Y solution in 100 ml volumetric flask and make up the volume to 100 ml with 1% w/v solution of hydrochloric acid.
    Examine the test solutions and reference solutions in diffused daylight by viewing down the vertical axes of the tubes against a white background.

    5. Fumaric acid By TLC

    Limit: Any spot corresponding to fumaric acid in the chromatogram obtained with test solution (a) is not more intense than the spot in the chromatogram obtained with reference solution (b) (1.5 percent)
    Procedure: Stationary Phase: Silica gel GF 254
    Test solution (a): Dissolve 0.5 g of the substance to be examined in acetone and dilute to 5 ml with the same solvent.
    Test solution (b): Dilute 1 ml of test solution (a) to 50 ml with acetone.
    Reference solution (a): Dissolve 20 mg of maleic acid WRS in acetone and dilute to 10 ml with the same solvent.
    Reference solution (b): Dissolve 15 mg of fumaric acid WRS in acetone and dilute to 10 ml with the same solvent.
    Reference solution (c): Mix 5 ml of the reference solution (a) and 5 ml of the reference solution (b).
    Apply separately to the plate 5 µl of test solutions (a) and (b), 5 µl of reference solutions (a) and (b) and 10 µl of the reference solution (c). Develop in a non-saturated tank over a path of 10 cm using a mixture of 12 volumes of anhydrous formic acid, 16 volumes of chloroform, 32 volumes of Butanol and 44 volumes of heptane. Dry the plate at 100°C for 15 min and examine in ultraviolet light at 254 nm. Any spot corresponding to fumaric acid in the chromatogram obtained with test solution (a) is not more intense than the spot in the chromatogram obtained with reference solution (b) (1.5 percent). The test is not valid unless the chromatogram obtained with reference solution (c) shows two clearly separated spots.

    6. Iron

    Limit: Not more than 5 ppm
    Procedure: To 10 ml of solution S add 2 ml of dilute hydrochloric acid and 0.05 ml of bromine water. After 5 min, remove the excess of bromine by passing a current of air and add 3 ml of potassium Thiocyanate solution. Shake. Prepare a standard at the same time and in the same manner, using a mixture of 5 ml of iron standard solution (1 ppm Fe), 1 ml of dilute hydrochloric acid, 6 ml of water and 0.05 ml of bromine water. Allow both solutions to stand for 5 min. Any red color in the test solution is not more intense than that in the standard (5 ppm).

    7. Heavy metals

    Limit: Not more than 10 ppm
    Reagent required
    Magnesium Oxide
    5M Hydrochloric acid
    Phenolphthalein
    13.5M Ammonia
    Lead standard solution (10 ppm Pb)
    Glacial acetic acid
    Standard Solution: Add 1ml of lead standard solution (10 ppm Pb) to 0.5 g of magnesium oxide contained in a silica crucible, dry the mixture in an oven at 100° to 105°. Ignite to dull red heat until a homogeneous white or grayish white mass is produced. If after 30 minutes of ignition the mixture remains colored, allow to cool, mix with a fine glass rod and repeat the ignition. If necessary, repeat the operation. Finally heat at 800° for about 1 hour, dissolve the residue using two 5-ml quantities of 5M hydrochloric acid. Add 0.1 ml of phenolphthalein solution and 13.5M ammonia dropwise 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.
    Sample Solution: Mix 1gm of the sample with 0.5 g of magnesium oxide in a silica crucible. Ignite to dull red heat until a homogeneous white or grayish white mass is produced. If after 30 minutes of ignition the mixture remains colored, allow to cool, mix with a fine glass rod and repeat the ignition. If necessary, repeat the operation. Finally heat at 800° for about 1 hour, dissolve the residue using two 5-ml quantities of 5M hydrochloric acid. Add 0.1 ml of phenolphthalein solution and 13.5M ammonia dropwise 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.
    Procedure: Any brown color produced by test solution is not more intense than that obtained by standard solution.

    8. Sulphated Ash

    Limit: Not more than 0.1%
    Procedure: Heat a silica crucible to redness for 10 min., allow cooling in desiccators and weighing. Place about 1 g of accurately weighed substance being examined in the silica crucible, moisten with sulphuric acid, ignite gently, again moisten with sulphuric acid and ignite at about 800°, cool, weigh again, ignite for 15 min. and repeat this procedure until two successive weighing do not differ by more than 0.5 mg.
    Calculation
                                        W3– W1
    % Sulphated ash = --------------- X 100
                                        W2 – W1
    Where:
    W1 = Weight of empty platinum crucible.
    W2 = Weight of crucible + sample.
    W3 = Weight of crucible + residue. (After ignition)

    9. Water

    Limit: Not more than 2.0%
    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 the mean value.
    Add accurately about 1gm. of the sample to the titration vessel. Allow titrating with KF reagent to the electrometric endpoint. Record the percentage of water content obtained by Karl Fischer titrator. Find out water content of the sample in triplicate and take mean value.

    10. Assay

    Limit: Not less than 99.0 % and not more than 101% on the anhydrous basis
    Procedure: Dissolve 0.500 g in 50 ml of water. Titrate with 1M sodium using 0.5 ml of phenolphthalein solution as indicator.
    1 ml of 1M sodium hydroxide is equivalent to 58.04 mg of C4H4O4.
    Calculation
                                                      B.R.x Actual molarity x 58.04 x 100 x 100
    % Assay on dried basis = -----------------------------------------------------------------
                                                      1 x Wt of sample in gm x (100-Water)

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