西安方昊化工有限公司

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].