Alkalinity—
To a 10.0-mL aliquot of the solution prepared in the test for
Acidity add 1 drop of
methyl red TS, and titrate with 0.01 N hydrochloric acid VS from a 10-mL buret. Perform a blank determination, and make any necessary correction. Not more than 1.0 mL of 0.010 N hydrochloric acid is required for each 1.0 g of Carbamazepine.
Chloride 
221
—
Boil 1.0 g with 20.0 mL of water for 10 minutes, cool, again adjust the volume, and filter: a 10.0-mL portion of the filtrate shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (0.014%).
Chromatographic purity—
Mobile phase and System suitability solution—
Proceed as directed in the
Assay.
Standard solution—
Dissolve accurately weighed quantities of
USP Carbamazepine RS, 10,11-dihydrocarbamazepine, and iminostilbene in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having known concentrations of about 0.02 mg per mL of each component. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with a mixture of methanol and water (50:50) to volume, and mix.
Test solution—
Transfer about 100 mg of Carbamazepine, accurately weighed, to a 50-mL volumetric flask, and dissolve in and dilute with methanol to volume. Transfer 25.0 mL of this solution to a 50-mL volumetric flask, add about 20 mL of water, and shake. Allow the mixture to cool to room temperature, and dilute with water to volume.
Chromatographic system
(see
Chromatography 621)—The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 1.5 mL per minute. Chromatograph the
System suitability solution, and record the peak responses as directed for
Procedure: the resolution,
R, between the 10,11-dihydrocarbamazepine and carbamazepine is not less than 1.70; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantities, in mg, of 10,11-dihydrocarbamazepine and iminostilbene in the portion of Carbamazepine taken by the formula:
100C(ri / rSi),
in which
C is the concentration, in mg per mL, of 10,11-dihydrocarbamazepine or iminostilbene in the
Standard solution; and
ri and
rSi are the peak responses obtained for either 10,11-dihydrocarbamazepine or iminostilbene from the
Test solution and the corresponding peak obtained from the
Standard solution, respectively. Calculate the quantities, in mg, of all other impurities found in the portion of Carbamazepine taken by the formula:
100C(ri / rS),
in which
ri is the peak response for any other impurity; and
rS is the peak response for carbamazepine obtained from the
Standard solution: not more than 0.2% of any individual impurity is found; and the total of all impurities (including 10,11-dihydrocarbamazepine and iminostilbene) is not more than 0.5%.
Assay—
Mobile phase—
Prepare a 1000-mL mixture of water, methanol, and tetrahydrofuran (85:12:3), add 0.22 mL of formic acid, mix, then add 0.5 mL of triethylamine, and mix. Filter and degas. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
System suitability solution—
Dissolve accurately weighed quantities of
USP Carbamazepine RS and 10,11-dihydrocarbamazepine in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having known concentrations of about 0.1 and 0.5 mg per mL, respectively. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, and dilute with a mixture of methanol and water (1:1) to volume.
Standard preparation—
Dissolve an accurately weighed quantity of
USP Carbamazepine RS in methanol, and dilute quantitatively with methanol to obtain a solution having a known concentration of about 2 mg per mL. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, and dilute with a mixture of methanol and water (1:1) to volume.
Assay preparation—
Transfer about 100 mg of Carbamazepine, accurately weighed, to a 50-mL volumetric flask, and dissolve in and dilute with methanol to volume. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, and dissolve in and dilute with a mixture of methanol and water (1:1) to volume.
Chromatographic system
(see
Chromatography 621)—The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 1.5 mL per minute. Chromatograph the
Standard preparation and the
System suitability solution, and record the peak responses as directed for
Procedure: the resolution,
R, between 10,11-dihydrocarbamazepine and carbamazepine in the
System suitability solution is not less than 1.70; and the relative standard deviation for replicate injections of the
Standard preparation is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C
15H
12N
2O in the portion of Carbamazepine taken by the formula:
500C(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Carbamazepine RS in the
Standard preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
;)
for 2 hours: it loses not more than 0.5% of its weight.