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Clidinium Bromide
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C22H26BrNO3 432.35
1-Azoniabicyclo[2.2.2]octane, 3-[(hydroxydiphenylacetyl)oxy]-1-methyl-, bromide, (±)-.
(±)-3-Hydroxy-1-methylquinuclidinium bromide benzilate [3485-62-9].
» Clidinium Bromide contains not less than 99.0 percent and not more than 100.5 percent of C22H26BrNO3, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers.
Identification—
A: Infrared Absorption 197K.
B: Dissolve about 250 mg in 5 mL of water in a test tube, cool in an ice bath, add 5 mL of trinitrophenol TS, and scratch the inner surface of the tube with a glass rod to induce crystallization. Collect the precipitate on a filter, wash with cold water, and dry at 105 for 1 hour: the picrate so obtained melts between 184 and 189, when tested by the method for Class I (see Melting Range or Temperature 741). [Caution—Picrates may explode. ]
C: To a solution of 100 mg in 2 mL of water add a few drops of 2 N nitric acid and 1 mL of silver nitrate TS: a yellowish white precipitate is formed.
Loss on drying 731— Dry it at 105 for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals 231— Dissolve 1.0 g in 25 mL of water: the limit is 0.002%.
Related compounds—
Adsorbent: 0.25-mm layer of chromatographic silica gel mixture.
Developing solvent system: a mixture of acetone, methanol, water, and hydrochloric acid (70:20:5:5).
Chromatographic plates— Predevelop suitable thin-layer chromatographic plates (see Thin-Layer Chromatography under Chromatography 621) by placing in a chromatographic chamber saturated with Developing solvent system, and allow the Developing solvent system to move about 15 cm. Remove the plates from the chamber, dry at 105 for 15 minutes, and cool.
Test solution— Dissolve 100 mg of Clidinium Bromide in 1.0 mL of 0.1 N methanolic hydrochloric acid.
Reference solution 1— Dissolve 3.0 mg of USP 3-Quinuclidinyl Benzilate RS in 100 mL of 0.1 N methanolic hydrochloric acid, and mix.
Reference solution 2— Dissolve 100 mg of USP Clidinium Bromide RS in 1.0 mL of 0.1 N methanolic hydrochloric acid, and add 20 µL of a solution of 25.0 mg of USP Clidinium Bromide Related Compound A RS in 1.0 mL of 0.1 N methanolic hydrochloric acid.
Standard solution— Dissolve 100 mg of USP Clidinium Bromide RS in 1.0 mL of 0.1 N methanolic hydrochloric acid.
Application volume: 20 µL.
Spray reagent— Dissolve 850 mg of bismuth subnitrate in a mixture of 10 mL of glacial acetic acid and 40 mL of water. In a separate container, dissolve 20 g of potassium iodide in 50 mL of water. Mix the two solutions, and dilute with dilute sulfuric acid (1 in 10) to 500 mL. Add 7.5 ± 2.5 g of iodine, and mix until solution is complete.
Procedure 1 (3-quinuclidinyl benzilate)— Apply the Standard solution, Reference solution 1, and the Test solution, as directed in the chapter. Place the plate in an unsaturated chromatographic chamber containing freshly prepared Developing solvent system, and allow the solvent front to move 10 cm. Remove the plate, dry at 105 for 10 minutes, cool, and spray with potassium iodoplatinate TS: the RF value of the principal spot obtained from the Test solution corresponds to that obtained from the Standard solution, and the Test solution shows no spot at an RF value (about 0.8) corresponding to that of 3-quinuclidinyl benzilate.
Procedure 2 (limit of clidinium bromide related compound A)— Apply Reference solution 2 and the Test solution to a second Chromatographic plate as directed in the chapter. Place the plate in an unsaturated chromatographic chamber containing freshly prepared Developing solvent system, and allow the solvent front to move 15 cm. Remove the plate, dry at 105 for 10 minutes, cool, and spray with Spray reagent. Any spot in the chromatogram obtained from the Test solution at an RF value of about 0.4 is not greater in size or intensity than the minor spot obtained from Reference solution 2: not more than 0.5% of clidinium bromide related compound A is found.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 1.2 g of Clidinium Bromide, accurately weighed, in 80 mL of glacial acetic acid, warming if necessary to effect solution. Cool, add 15 mL of mercuric acetate TS, and titrate with 0.1 N perchloric acid in dioxane 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 43.24 mg of C22H26BrNO3.
Auxiliary Information— Staff Liaison : Elena Gonikberg, Ph.D., Scientist
Expert Committee : (MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
USP29–NF24 Page 535
Pharmacopeial Forum : Volume No. 27(4) Page 2720
Phone Number : 1-301-816-8251