Chlorhexidini digluconatis solutio - DrugFuture

1 Chlorhexidine digluconate solutionEUROPEAN PHARMACOPOEIA acid Rand 20 mL ofdilute hydrochloric acid Rinstead of the solution of the substance to be ( ).Test the mobile phase and dilute to 100 mL with the mobile solution (a).Dissolve15mgofchlorhexidinefor performance test CRSin the mobile phase and dilute mL with the mobile solution (b). mL with the mobile solution (c). (b) 10 mL with the mobile : size:l= , =4mm; stationary phase:octadecylsilyl silica gel forchromatography R(5 m).Mobile octanesulfonate Rinamixtureof120mLofglacial acetic acid R,270mLofwater Rand 730 mL ofmethanol : spectrophotometer at 254 : with the mobile phase for at least 1 :10 time: 6 times the retention time of suitability: reference solution (a): the chromatogram obtained is similar to the chromatogramsupplied withchlorhexidine for performance test CRSin that the peaks due to impurity A and impurity Bprecede that due to chlorhexidine; if necessary, adjust theconcentration of acetic acid in the mobile phase (increasingthe concentration decreases the retention times).

2 Limits: total: not more than the area of the principal peak in thechromatogram obtained with reference solution (b) ( percent); disregard limit: the area of the principal peak in thechromatogram obtained with reference solution (c) ( percent); disregard any peak with a relative retention time withreference to chlorhexidine of or on drying( ): maximum per cent, determined g by drying in an oven at 105 ash( ): maximum per cent, determined g in 100 mL ofanhydrous acetic acid Randtitrate M perchloric acid. Determine the end-pointpotentiometrically ( ). M perchloric acidis equivalent to mgof 1-(4-chlorophenyl)-5-[6-[(cyanocarbamimi doyl)amino]-hexyl]biguanide,B. [[6-[[[(4-chlorophenyl)carbamimidoyl]car bamimidoyl]-amino]hexyl]carbamimidoyl]ur ea,C. 1,1 -[hexane-1,6-diylbis(iminocarbonimidoyl) ]bis[3-(4-chlorophenyl)urea],D.

3 1,1 -[[[[(4-chlorophenyl)carbamimidoyl]imino ]methylene]-bis[imino(hexane-1,6-diyl)]] bis[5-(4-chlorophenyl)biguanide].01/2008 :0658corrected DIGLUCONATESOLUTIONC hlorhexidini digluconatis solutioC34H54Cl2N10O14Mr898[18472-51-0]D EFINITIONA queous solution of 1,1 -(hexane-1,6-diyl)bis[5-(4-chlorophenyl) biguanide] : 190 g/L to 210 : almost colourless or pale-yellowish : miscible with water, with not more than 3 parts ofacetone and with not more than 5 parts of ethanol (96 per cent).IDENTIFICATIONF irst identification: A, identification: B, C, Infrared absorption spectrophotometry ( ).Preparation:to1mLadd40mLofwater R, cool in icedwater, make alkaline totitan yellow paper Rby addingdropwise, and with stirring,strong sodium hydroxidesolution Rand add 1 mL in excess. Filter, wash the1660 See the information section on general monographs (cover pages)EUROPEAN PHARMACOPOEIA digluconate solutionprecipitate withwater Runtil the washings are free fromalkali and recrystallise fromethanol (70 per cent V/V) at 100-105 C.

4 Examine the :chlorhexidine Thin-layer chromatography ( ).Test solution. Dilute mL of the preparation to beexamined to 50 mL withwater CRSin 1 mL ofwater :TLC silica gel G plate phase:concentrated ammonia R,ethyl acetate R,water R,ethanol (96 per cent) R(10:10:30:50V/V/V/V).Application:5 :at100 :spraywitha50g/Lsolutionofpotassiumdichr omate Rin a 40 per centm/msolution ofsulfuricacid : after 5 min, the principal spot in the chromatogramobtained with the test solution is similar in position, colourand size to the principal spot in the chromatogram obtainedwith the reference To 1 mL add 40 mL ofwater R, cool in iced water, makealkaline totitan yellow paper Rby adding dropwise, andwith stirring,strong sodium hydroxide solution Rand add1 mL in excess. Filter, wash the precipitate withwater Runtilthewashingsarefreefromalkaliandrec rystallisefromethanol (70 per cent V/V) R.

5 Dry at 100-105 C. The residuemelts ( )at132 Cto136 To mL add 5 mL of a 10 g/L solution ofcetrimide R,1mLofstrong sodium hydroxide solution Rand 1 mL ofbromine water R; a deep red colour is density( ): to ( ): to mL to 100 mL withcarbon dioxide-free water : maximum per cent, calculated withreference to chlorhexidine digluconate at a nominalconcentration of 200 mL to 100 mL withwater mL ofdilute hydrochloric acid Rand dilute to 20 mLwithwater R. Add rapidly and with thorough mixing after eachaddition: mL ofsodium nitrite solution R, 2 mL of a50 g/L solution ofammonium sulfamate R,5mLofa1g/Lsolution ofnaphthyle thylenediamine dihydrochloride R,1mLofethanol (96 per cent) R; dilute to mL withwater Rand allow to stand for 30 min. Any reddish-blue colour in thesolution is not more intense than that in a standard mL of a g/L solution ofchloroaniline Rindilutehydrochloric acid Rand 10 mL ofwater Rinstead of thedilution of the preparation to be ( ).

6 Test mL with the mobile phase. Dilute mL of this solutionto mL with the mobile solution (a).Dissolve15mgofchlorhexidinefor performance test CRSin the mobile phase and dilute mL with the mobile solution (b). mL with the mobile solution (c). (b)to 50 mL with the mobile : size:l= , =4mm; stationary phase:octadecylsilyl silica gel forchromatography R(5 m).Mobile octanesulfonate Rinamixtureof120mLofglacial acetic acid R, 270 mL ofwater Rand 730mLofmethanol : spectrophotometer at 254 :10 time: 6 times the retention time of suitability: reference solution (a): the chromatogram obtained is similar to the chromatogramsupplied withchlorhexidine for performance test CRSinthat the peaks due to impurity A and impurity Bprecede that due to chlorhexidine; if necessary, adjust theconcentration of acetic acid in the mobile phase (increasingthe concentration decreases the retention times).

7 Limits: total: not more than the area of the principal peak in thechromatogram obtained with reference solution (b) ( percent); disregard limit: the area of the principal peak in thechromatogram obtained with reference solution (c) ( percent); disregard any peak with a relative retention time withreference to the principal peak of or the density ( ) of the preparation to be g to a 250 mL beaker and add 50 mL ofanhydrousacetic acid M perchloric acid. Determinethe end-point potentiometrically ( ). M perchloric acidis equivalent to mgof from 1-(4-chlorophenyl)-5-[6-[(cyanocarbamimi doyl)amino]-hexyl]biguanide,B. [[6-[[[(4-chlorophenyl)carbamimidoyl]car bamimidoyl]-amino]hexyl]carbamimidoyl]ur ea,C. 1,1 -[hexane-1,6-diylbis(iminocarbonimidoyl) ]bis[3-(4-chlorophenyl)urea],General Notices (1) apply to all monographs and other texts1661 Chlorhexidine dihydrochlorideEUROPEAN PHARMACOPOEIA 1,1 -[[[[(4-chlorophenyl)carbamimidoyl]imino ]methylene]-bis[imino(hexane-1,6-diyl)]] bis[5-(4-chlorophenyl)biguanide].

8 01/2008:0659corrected DIHYDROCHLORIDEC hlorhexidini [3697-42-5]DEFINITION1,1 -(Hexane-1,6-diyl)bis[5-(4-chlorophenyl) biguanide] : per cent to per cent (dried substance).CHARACTERSA ppearance: white or almost white, crystalline : sparingly soluble in water and in propylene glycol,very slightly soluble in ethanol (96 per cent).IDENTIFICATIONF irst identification: A, identification: B, C, Infrared absorption spectrophotometry ( ).Comparison:chlorhexidine dihydrochloride Dissolve about 5 mg in 5 mL of a warm 10 g/L solutionofcetrimide Rand add 1 mL ofstrong sodium hydroxidesolution Rand 1 mL ofbromine water R. A dark red colouris Dissolve g in 10 mL of a mixture of equal volumes ofhydrochloric acid Randwater R,filter if necessary and cool in iced water. Make alkaline totitan yellow paper Rby adding dropwise, and with stirring,strong sodium hydroxide solution Rand add 1 mL in , wash the precipitate withwater Runtil the washingsarefreefromalkaliandrecrystallis efromethanol (70 percent V/V) R.

9 Dry at 100-105 C. The residue melts ( )at 132 C to 136 It gives reaction (a) of chlorides ( ).TESTSC hloroaniline: maximum 500 g add 1 mL ofhydrochloric acid R,shakeforabout30 s, dilute to 30 mL withwater Rand shake until a clearsolution is obtained. Add rapidly and with thorough mixingafter each addition: mL ofdilute hydrochloric acid R, mL ofsodium nitrite solution R, 2 mL of a 50 g/L solutionofammonium sulfamate R, 5 mL of a g/L solution ofnaphthylethylenediamine dihydrochloride Rand 1 mL ofethanol (96 per cent) R; dilute to mL withwater Randallow to stand for 30 min. Any reddish-blue colour in thesolution is not more intense than that in a standard mL of a g/L solution ofchloroaniline Rindilutehydrochloric acid Rand 20 mL ofdilute hydrochloric acid Rinstead of the solution of the substance to be substances.

10 Liquid chromatography ( ).Test the mobile phase and dilute to 100 mL with the mobile solution (a).Dissolve15mgofchlorhexidinefor performance test CRSin the mobile phase and dilute mL with the mobile solution (b). mL with the mobile solution (c). Dilute mL of reference solution (b) 10 mL with the mobile : size:l= , =4mm; stationary phase:octadecylsilyl silica gel forchromatography R(5 m).Mobile octanesulfonate Rinamixtureof120mLofglacial acetic acid R, 270 mL ofwater Rand 730 mL ofmethanol : spectrophotometer at 254 : with the mobile phase for at least 1 :10 time: 6 times the retention time of suitability: reference solution (a): the chromatogram obtained is similar to the chromatogramsupplied withchlorhexidine for performance test CRSin that the peaks due to impurity A and impurity Bprecede that due to chlorhexidine; if necessary, adjust theconcentration of acetic acid in the mobile phase (increasingthe concentration decreases the retention times).