Chlordiazepoxide Capsules

General Notices

Action and use

Benzodiazepine.

Definition

Chlordiazepoxide Capsules contain Chlordiazepoxide Hydrochloride.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of chlordiazepoxide hydrochloride, C₁₆H₁₄ClN₃O,HCl

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the following procedure protected from light. Shake a quantity of the mixed capsule contents containing 20 mg of Chlordiazepoxide Hydrochloride with 150 mL of 0.1m hydrochloric acid for 20 minutes. Add sufficient 0.1 m hydrochloric acid to produce 200 mL and filter. Dilute 10 mL of the filtrate to 100 mL with 0.1Mhydrochloric acid. The light absorption, Appendix II B, in the range 230 to 350 nm exhibits two maxima, at 246 nm and 308 nm.

B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions

(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.

(b) Use 900 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.

procedure

After 45 minutes withdraw a sample of the medium and measure the absorbance of a layer of suitable thickness of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 308 nm, Appendix II B using 0.1m hydrochloric acid in the reference cell.

determination of content

Calculate the total content of chlordiazepoxide hydrochloride, C₁₆H₁₄ClN₃O,HCl, in the medium taking 292 as the value of A(1%, 1 cm) at the maximum at 308 nm.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared immediately before use and protected from light.

(1) Shake a quantity of the mixed capsule contents containing 20 mg of Chlordiazepoxide Hydrochloride with 50 mL of the mobile phase, dilute to 100 mL with the mobile phase and filter.

(2) Dilute 3 volumes of solution (1) to 100 volumes with the mobile phase.

(3) Dilute 2 volumes of solution (1) to 100 volumes with the mobile phase and dilute 1 volume of this solution to 10 volumes with the mobile phase.

(4) 0.00004% w/v of aminochlorobenzophenone (impurity C) in the mobile phase.

(5) 0.0002% w/v of chlordiazepoxide impurity A EPCRS and 0.0002% w/v of chlordiazepoxide hydrochloride BPCRS in the mobile phase.

chromatographic conditions

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Waters Symmetry C18 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 254 nm.

(f) Inject 10 µL of each solution.

(g) For solutions (1) and (4) allow the chromatography to proceed for 6 times the retention time of the peak due to chlordiazepoxide.

mobile phase

Equal volumes of acetonitrile and water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between the peaks due to impurity A and chlordiazepoxide is at least 5.0.

When the chromatograms are recorded under the prescribed conditions the retention times relative to chlordiazepoxide (retention time about 3.6 min) are impurity A, about 0.7 and impurity C, about 3.9.

limits

In the chromatogram obtained with solution (1):

the area of any peak due to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (3%);

the area of any peak due to impurity C is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.2%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);

the sum of the impurities is not greater than 3.4%.

Disregard any peak with an area less than half the area of the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared immediately before use and protected from light.

(1) Shake a quantity of the mixed contents of 20 capsules containing 20 mg of Chlordiazepoxide Hydrochloride with 50 mL of the mobile phase, dilute to 100 mL with the mobile phase and filter. Dilute 10 mL of this solution to 100 mL with the mobile phase.

(2) 0.002% w/v of chlordiazepoxide hydrochloride BPCRS in the mobile phase.

(3) 0.0002% w/v of chlordiazepoxide impurity A EPCRS and 0.0002% w/v chlordiazepoxide hydrochloride BPCRS in mobile phase.

chromatographic conditions

The chromatographic conditions described under Related substances may be used.