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This is a revised draft proposal for The International Pharmacopoeia (Working document QAS/15.608/Rev.1, December 2015).
The working document with line numbers and tracked changes is available for comment at www.who.int/medicines/areas/qualitv safetv/qualitv assurance/projects/en/. Please address any comments to: World Health Organization, Quality Assurance and Safety: Medicines, Dr Herbert Schmidt, 1211 Geneva 27, Switzerland; fax: +41 22 791 4730; email: [email protected].
[Note from the Secretariat. It is proposed to revise the monograph on Carbamazepine in The International Pharmacopoeia. Comments are in particular sought as to whether the impurities listed under the section Impurities are degradation products or synthesis impurities.]
[Note from the editor. In accordance with WHO editorial policy the text reproduced below does not include tracked changes. Changes from the current monograph are indicated by insert and delete in the working document available at the above-mentioned web address.]
Molecular formula. C15H12N20
Relative molecular mass. 236.3
Graphic formula.
Chemical name. 57/-Dibenz[b,/]azepine-5-carboxamide; CAS Reg. No. 298-46-4. Description. A white to almost white, crystalline powder.
Solubility. Very slightly soluble in water; sparingly soluble in acetone; soluble in ethanol (-750 g/L) TS; freely soluble in dichloromethane.
Category. Antiepileptic.
Additional information. Carbamazepine exhibits polymorphism. The acceptable crystalline form is anhydrous polymorph form III1. It corresponds to carbamazepine RS.
Storage. Carbamazepine should be kept in a tightly closed container.
Requirements
Definition. Carbamazepine contains not less than 98.0% and not more than 102.0% of C15H12N20, calculated with reference to the dried substance.
Identity tests
* Either test A or any two of tests B, C and D may be applied.
A. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum obtained from the test substance without pretreatment is concordant with the spectrum obtained from carbamazepine RS or with the reference spectrum of carbamazepine.
B. Carry out test B.1 or, where UV detection is not available, test B.2.
B.1. Carry out the test as described under 1.14.1 Thin-laver chromatography using silica gel R6 as the coating substance and a mixture of 78 volumes of toluene R and 22 volumes of methanol R as the mobile phase. Apply separately to the plate 2 pL of each of the following three solutions, prepared using a mixture of equal volumes of ethanol (-750 g/L) TS and dichloromethane R. For...