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Clemastine Fumarate
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C21H26ClNO·C4H4O4 459.96

Pyrrolidine, 2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methyl-, [R-(R*,R*)]-, (E)-2-butenedioate (1:1).
(+)-(2R)-2-[2-[[[(R)-p-Chloro--methyl--phenylbenzyl]-oxy]ethyl]-1-methylpyrrolidine fumarate (1:1) [14976-57-9].
» Clemastine Fumarate contains not less than 98.0 percent and not more than 102.0 percent of C21H26ClNO·C4H4O4, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers, at a temperature not exceeding 25.
Clarity and color of solution— Dissolve 100 mg of Clemastine Fumarate in 10.0 mL of methanol, and mix to obtain the Test solution. Prepare a Comparison solution by mixing 2.5 mL of 0.00002 M sodium chloride, 2.5 mL of water, 5.0 mL of 2.5 N nitric acid, and 1.0 mL of 0.1 N silver nitrate, and use this solution within 5 minutes. Prepare a Color matching fluid by mixing 1 volume of Matching Fluid C (see Color and Achromicity 631) with 3 volumes of water. Transfer the Test solution, the Comparison solution, and 10 mL of Color matching fluid to separate test tubes having the same nominal diameter (about 12 mm). View the Test solution and the Comparison solution horizontally against a dull black background: the Test solution is clear or not more opalescent than the Comparison solution. View the Test solution and Color matching fluid horizontally against a dull white background: the Test solution is colorless or not more intensely colored than Color matching fluid.
Identification—
B: Prepare a Test preparation by dissolving 40 mg of Clemastine Fumarate in 2.0 mL of dilute alcohol (8 in 10) with slight warming. Similarly prepare a Standard preparation by dissolving 50 mg of fumaric acid in 10.0 mL of dilute alcohol (8 in 10). Separately apply 5-µL portions of the Test preparation and the Standard preparation to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture, and dry the spots with the aid of a current of air. Develop the chromatogram in a solvent system consisting of a mixture of diisopropyl ether, formic acid, and water (70:25:5) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, dry at 100 for 30 minutes, cool, and spray the plate with 0.1 M potassium permanganate. Dry briefly with the aid of a current of warm air, and examine the chromatogram: the principal spot obtained from the Test preparation corresponds in RF value, color, and intensity to that obtained from the Standard preparation.
Specific rotation 781S: between +15.0 and +18.0 (t = 20).
Test solution: 10 mg per mL, in methanol.
pH 791: between 3.2 and 4.2, in a suspension (1 in 10).
Loss on drying 731— Dry it at 105 to constant weight: it loses not more than 0.5% of its weight.
Heavy metals, Method II 231: 0.002%.
Chromatographic purity—
Spray reagent— Dissolve 850 mg of bismuth subnitrate in a mixture of 10 mL of glacial acetic acid and 40 mL of water, and mix (Solution A). Dissolve 8 g of potassium iodide in 20 mL of water (Solution B). Mix 5.0 of Solution A, 5.0 mL of Solution B, and 20 mL of glacial acetic acid in a 100-mL volumetric flask, dilute with water to volume, and mix.
Standard preparation— Dissolve a suitable quantity of USP Clemastine Fumarate RS in a mixture of chloroform and methanol (1:1) to obtain a solution having a known concentration of 20 mg per mL. Dilute portions of this solution quantitatively with the mixture of chloroform and methanol (1:1) to prepare 5 Comparison solutions having known concentrations of 0.10, 0.08, 0.06, 0.04, and 0.02 mg per mL, respectively (0.5%, 0.4%, 0.3%, 0.2%, and 0.1% of the Standard preparation, respectively).
Test preparation— Dissolve 100 mg of Clemastine Fumarate in 5.0 mL of a mixture of chloroform and methanol (1:1), and mix.
Procedure— Separately apply 5-µL portions of the Standard preparation, each of the 5 Comparison solutions, and the Test preparation to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of chloroform, methanol, and ammonium hydroxide (90:10:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and dry the plate at room temperature with the aid of a current of air. Locate the spots on the plate by spraying first with Spray reagent, then with 3% hydrogen peroxide: the principal spot obtained from the Test preparation corresponds in RF value, color, and intensity to that obtained from the Standard preparation; the sum of the intensities of any secondary spots, if present in the chromatogram from the Test preparation, corresponds to not more than 1.0%; and the intensities of any secondary spots do not exceed 0.5% of that of the principal spot in the chromatogram from the Standard preparation on the basis of comparison with spots obtained from the Comparison solutions.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Transfer about 350 mg of Clemastine Fumarate, accurately weighed, to a small conical flask, and dissolve in 60 mL of glacial acetic acid. Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 46.00 mg of C21H26ClNO·C4H4O4.
Auxiliary Information— Staff Liaison : Daniel K. Bempong, Ph.D., Scientist
Expert Committee : (MDPS05) Monograph Development-Pulmonary and Steroids
USP29–NF24 Page 533
Phone Number : 1-301-816-8143