Chlorhexidine Gluconate solution
C22H30Cl2N10,2C6H12O7 898 18472-51-0
Action and use
Antiseptic.
Preparations
Chlorhexidine Gluconate Eye Drops
Chlorhexidine Gluconate Gel
Chlorhexidine Irrigation Solution
Chlorhexidine Mouthwash
Lidocaine and Chlorhexidine Gel
DEFINITION
Aqueous solution of 1,1?-(hexane-1,6-diyl)bis[5-(4-chlorophenyl)biguanide] di-D- gluconate.
Content
190 g/L to 210 g/L.
CHARACTERS
Appearance
Almost colourless or pale-yellowish liquid.
Solubility
Miscible with water, with not more than 3 parts of acetone and with not more than 5 parts of ethanol (96 per cent).
IDENTIFICATION
First identification A, B.
Second identification B, C, D.
A. Infrared absorption spectrophotometry (2.2.24).
Preparation To 1 mL add 40 mL of water R, cool in iced water, make alkaline to titan yellow paper R by adding dropwise, and with stirring, strong sodium hydroxide solution R and add 1 mL in excess. Filter, wash the precipitate with water R until the washings are free from alkali and recrystallise from ethanol (70 per cent V/V) R. Dry at 100-105 癈. Examine the residue.
Comparison chlorhexidine CRS.
B. Thin-layer chromatography (2.2.27).
Test solution Dilute 10.0 mL of the preparation to be examined to 50 mL with water R.
Reference solution Dissolve 25 mg of calcium gluconate CRS in 1 mL of water R.
Plate TLC silica gel G plate R.
Mobile phase concentrated ammonia R, ethyl acetate R, water R, ethanol (96 per cent) R (10:10:30:50 V/V/V/V).
Application 5 μL
Development Over a path of 10 cm.
Drying At 100℃ for 20 min and allow to cool.
Detection Spray with a 50 g/L solution of potassium dichromate R in a 40 per cent m/m solution of sulfuric acid R.
Results After 5 min, the principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with the reference solution.
C. To 1 mL add 40 mL of water R, cool in iced water, make alkaline to titan yellow paper R by adding dropwise, and with stirring, strong sodium hydroxide solution R and add 1 mL in excess. Filter, wash the precipitate with water R until the washings are free from alkali and recrystallise from ethanol (70 per cent V/V) R. Dry at 100-105℃. The residue melts (2.2.14) at 132℃ to 136 ℃.
D. To 0.05 mL add 5 mL of a 10 g/L solution of cetrimide R, 1 mL of strong sodium hydroxide solution R and 1 mL of bromine water R; a deep red colour is produced.
TESTS
Relative density (2.2.5)
1.06 to 1.07.
pH (2.2.3)
5.5 to 7.0.
Dilute 5.0 mL to 100 mL with carbon dioxide-free water R.
Chloroaniline
Maximum 0.25 per cent, calculated with reference to chlorhexidine digluconate at a nominal concentration of 200 g/L.
Dilute 2.0 mL to 100 mL with water R. To 10 mL of this solution add 2.5 mL of dilute hydrochloric acid R and dilute to 20 mL with water R. Add rapidly and with thorough mixing after each addition: 0.35 mL of sodium nitrite solution R, 2 mL of a 50 g/L solution of ammonium sulfamate R, 5 mL of a 1 g/L solution of naphthyle thylenediamine dihydrochloride R, 1 mL of ethanol (96 per cent) R; dilute to 50.0 mL with water R and allow to stand for 30 min. Any reddish-blue colour in the solution is not more intense than that in a standard prepared at the same time and in the same manner using a mixture of 10.0 mL of a 0.010 g/L solution of chloroaniline R in dilute hydrochloric acid R and 10 mL of water R instead of the dilution of the preparation to be examined.
Related substances
Liquid chromatography (2.2.29).
Test solution Dilute 5.0 mL of the preparation to be examined to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase.
Reference solution (a) Dissolve 15 mg of chlorhexidine for performance test CRS in the mobile phase and dilute to 10.0 mL with the mobile phase.
Reference solution (b) Dilute 3.0 mL of the test solution to 100 mL with the mobile phase.
Reference solution (c) Dilute 1.0 mL of reference solution (b) to 50 mL with the mobile phase.
Column:
— size: l = 0.2 m, ?= 4 mm;
— stationary phase: octadecylsilyl silica gel for chromatography R (5 祄).
Mobile phase Solution of 2.0 g of sodium octanesulfonate R in a mixture of 120 mL of glacial acetic acid R, 270 mL of water R and 730 mL of methanol R.
Flow rate 1.0 mL/min.
Detection Spectrophotometer at 254 nm.
Equilibration With the mobile phase for at least 1 hour.
Injection 10 μL
Run time: 6 times the retention time of chlorhexidine.
System suitability Reference solution (a):
— the chromatogram obtained is similar to the chromatogram supplied with chlorhexidine for performance test CRS in that the peaks due to impurity A and impurity B precede that due to chlorhexidine; if necessary, adjust the concentration of acetic acid in the mobile phase (increasing the concentration decreases the retention times).
Limits:
— total: not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (3.0 per cent);
— disregard limit: the area of the principal peak in the chromatogram obtained with reference solution (c) (0.06 per cent); disregard any peak with a relative retention time with reference to the principal peak of 0.25 or less.
ASSAY
Determine the density (2.2.5) of the preparation to be examined. Transfer 1.00 g to a 250 mL beaker and add 50 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid . Determine the end-point potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 22.44 mg of C34H54Cl2N10O14.
STORAGE
Protected from light.
IMPURITIES
A. 1-(4-chlorophenyl)-5-[6-[(cyanocarbamimidoyl)amino]hexyl]biguanide,
B. [[6-[[[(4- chlorophenyl)carbamimidoyl]carbamimidoyl]amino]hexyl]carbamimidoyl]urea,
C. 1,1’-[hexane-1,6-diylbis(iminocarbonimidoyl)]bis[3-(4-chlorophenyl)urea],
D. 1,1’-[[[[(4-chlorophenyl)carbamimidoyl]imino]methylene]bis[imino(hexane-1,6- diyl)]]bis[5-(4-chlorophenyl)biguanide].