Chlordiazepoxide Hydrochloride Capsules

» Chlordiazepoxide Hydrochloride Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C16H14ClN3O·HCl.

Packaging and storage— Preserve in tight, light-resistant containers.

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USP 2-Amino-5-chlorobenzophenone RS

C13H10ClNO 231.68

USP Chlordiazepoxide Hydrochloride RS

USP Chlordiazepoxide Related Compound A RS

7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide.
C15H11ClN2O2 286.72

Identification—

A: Transfer a portion of the Capsule powder, equivalent to about 60 mg of chlordiazepoxide hydrochloride, to a 100-mL flask. Add methanol to volume, mix, and filter, discarding the first 15 mL of the filtrate. Pipet 5 mL of the clear filtrate into a 100-mL volumetric flask, and add a 1 in 360 solution of sulfuric acid in dehydrated alcohol to volume. Pipet 10 mL of this solution into a 50-mL volumetric flask, and dilute with the same acidified alcohol to volume. The resulting solution exhibits maxima at 245 ± 2 nm and 311 ± 2 nm, and the ratio A245/A311 is between 2.90 and 3.45, using the acidified alcohol as the blank and a 1-cm cell.

B: A portion of the contents of Capsules responds to Identification test C under Chlordiazepoxide Hydrochloride.

Dissolution

711

—

Medium: water; 900 mL.

Apparatus 1: 100 rpm.

Time: 30 minutes.

Procedure— Measure the amount in solution in filtered portions of the Dissolution Medium, suitably diluted, in 1-cm cells at the wavelength of maximum absorbance at about 245 nm, with a suitable spectrophotometer, in comparison with a Standard solution of known concentration of USP Chlordiazepoxide Hydrochloride RS. Remove the contents of 12 Capsules as completely as possible with the aid of a current of air. Dissolve the empty capsule shells in 900 mL of Dissolution Medium. Filter a portion of the solution, and determine the absorbance at the same dilution and in the same manner as for the Capsules, making any necessary modifications.

Tolerances— Not less than 85% (Q) of the labeled amount of C16H14ClN3O·HCl is dissolved in 30 minutes.

Uniformity of dosage units

905

: meet the requirements.

Procedure for content uniformity— [note—Use low-actinic glassware in this procedure. ] Transfer the contents of 1 Capsule to a 200-mL volumetric flask, dissolve in and dilute with water to volume, and filter, discarding the first 20 mL of the filtrate. Dilute a portion of the filtrate quantitatively and stepwise with 0.1 N hydrochloric acid to obtain a solution having a concentration of about 6 µg of chlordiazepoxide hydrochloride per mL. Dissolve a suitable quantity of USP Chlordiazepoxide Hydrochloride RS, accurately weighed, in 0.1 N hydrochloric acid to obtain a Standard solution having a known concentration of about 6 µg per mL. Concomitantly determine the absorbances of the two solutions in 1-cm cells at the wavelength of maximum absorbance at about 245 nm, with a suitable spectrophotometer, using 0.1 N hydrochloric acid as the blank. Calculate the quantity, in mg, of C16H14ClN3O·HCl in the Capsule by the formula:

(T / D)C(AU / AS)

in which T is the labeled quantity, in mg, of chlordiazepoxide hydrochloride in the Capsule; D is the concentration, in µg per mL, of chlordiazepoxide hydrochloride in the test solution, based on the labeled quantity per Capsule and the extent of dilution; C is the concentration, in µg per mL, of USP Chlordiazepoxide Hydrochloride RS in the Standard solution; and AU and AS are the absorbances of the solution from the contents of the Capsule and the Standard solution, respectively.

Related compounds— Proceed as directed for Related compounds under Chlordiazepoxide Hydrochloride, but use an accurately weighed portion of Capsule contents, equivalent to about 25 mg of chlordiazepoxide hydrochloride, and use 15 µL of a 1 in 1000 solution of USP Chlordiazepoxide Related Compound A RS in acetone and 10 µL of a 1 in 20,000 solution of USP 2-Amino-5-chlorobenzophenone RS in acetone. Not more than 3.0% of chlordiazepoxide related compound A is found, and not more than 0.1% of 2-amino-5-chlorobenzophenone is found.

Assay— [note—Use low-actinic glassware in this procedure. ] Proceed as directed in the Assay under Chlordiazepoxide Tablets except to use an accurately weighed portion of capsule contents equivalent to about 5 mg of chlordiazepoxide hydrochloride and USP Chlordiazepoxide Hydrochloride RS in preparing the Standard preparation.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Ravi Ravichandran, Ph.D. Principal Scientific Liaison 1-301-816-8330	(SM42010) Monographs - Small Molecules 4
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 2619