Content area
Full text
(Kalii clavulanas)
This is a draft proposal of a revised monograph for The International Pharmacopoeia (Working document QAS/16.681, February 2018). The working document with line numbers is available for comment at www.who.int/medicines/ areas/qualitv safety/quality assurance/projects.
[Note from the Secretariat. It is proposed to include the monograph on Clavulanate potassium in The International Pharmacopoeia. The monograph is based on laboratory investigations and on information found in the Chinese Pharmacopoeia, the European Pharmacopoeia and the United States Pharmacopeia. Comments are in particular sought regarding the nature of the impurities listed on the transparency list, i.e. whether they are synthesis-related impurities, degradation products or both.]
Molecular formula. C8H8KNO5.
Relative molecular mass. 237.3.
Chemical name. Potassium (2Æ,3Z,5Æ)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1azabicyclo[3.2.0]heptane-2-carboxylate, CAS Reg. No.61177-45-5.
Description. A white or almost white, crystalline powder.
Solubility. Freely soluble in water R, slightly soluble in ethanol (~710 g/L) TS, very slightly soluble in acetone R.
Category. ß-Lactamase inhibitor.
Storage. Potassium clavulanate should be kept in tightly closed containers, protected from light, at a temperature of 2°C to 8°C.
Additional information. Potassium clavulanate is hygroscopic.
Requirements
Definition. Potassium clavulanate contains not less than 96.5% and not more than 102.0% of C8H8KNO5, calculated with reference to the anhydrous substance.
Manufacture. The method of production is validated to demonstrate that the substance, if tested, would comply with the limit of not more than 0.01% for clavam-2-carboxylate using a suitable method.
Identity tests
Either tests A and D or 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 is concordant with the reference spectrum of potassium clavulanate.
B. Carry out the test as described under 1.14.4 High-performance liquid chromatography using the conditions given under "Assay". The retention time of the principal peak in the chromatogram obtained from solution (1) is similar to that obtained from solution (2).
C. [Note from the Secretariat. It is intended to add a TLC test specific for clavulanic acid and amoxicilline.]
D. Ignite a small quantity, dissolve the residue in water and filter. Add 2 mL of sodium hydroxide (~80 g/L) TS to the filtrate. It yields the reaction described under 2.1 General identification tests as characteristic of potassium.
Solution S. Dissolve 0.400 g of the test substance in...