CODEINE - uspbpep.com

1 Cocoyl caprylocaprateEUROPEAN PHARMACOPOEIA stearic acid ( ): per cent to per cent, oleic acid and isomers ( ): per cent to percent, linoleic acid ( ): per cent to per cent, linolenic acid ( ) , arachidic acid ( ) , eicosenoic acid ( ) in a well-filled container, protected from :1411 COCOYL CAPRYLOCAPRATEC ocoylis caprylocaprasDEFINITIONM ixtureofestersofsaturatedC12-C18alcohols with caprylic(octanoic) and capric (decanoic) acids obtained by thereaction of these acids with vegetable saturated : slightly yellowish : practically insoluble in water, miscible withethanol (96 per cent) and with liquid density: about index: about :about11mPa Freezing point ( ): maximum 15 Infrared absorption spectrophotometry ( ).

2 Comparison:cocoyl caprylocaprate Composition of fatty acids and fatty alcohols (see Tests).TESTSA ppearance. The substance to be examined is not moreintensely coloured than reference solution Y5( ,Method I).Acid value( ): maximum , determined on value( , Method A): maximum value( , Method A): maximum value( ): 160 to of fatty acids and fatty alcohols( ,Method C). Use the chromatogram obtained with thefollowing reference solution for identification of the peaksdue to the fatty the amounts of the substanceslisted in the following table in 10 ml ofheptane (mg)

3 Methyl caproate R10 Methyl caprylate R90 Methyl caprate R50 Methyl laurate R20 Methyl myristate R10 Methyl palmitate R10 Methyl stearate R10 Capric alcohol R10 Lauryl alcohol R100 Myristyl alcohol R40 Cetyl alcohol CRS30 Stearyl alcohol CRS20 Considerthesumoftheareasofthepeaksduetot hefattyacids listed below to be equal to 100 and the sum of theareas of the peaks due to the fatty alcohols listed below tobe equal to of the fatty acid fraction of the substance: caproic , caprylic acid: per cent to per cent, capric acid: per cent to per cent, lauric , myristic of the fatty alcohol fraction of the substance: capric , lauryl alcohol: per cent to per cent, myristyl alcohol: per cent to per cent, cetyl alcohol: per cent to per cent, stearyl ( ): maximum per cent, determined on ash( ): maximum per cent, determined :0076corrected , ,8-Didehydro-4,5 -epoxy-3-methoxy-17-methylmorphinan-6 : per cent to per cent (dried substance).

4 1594 See the information section on general monographs (cover pages)EUROPEAN PHARMACOPOEIA : white or almost white, crystalline powder orcolourless : soluble in boiling water, freely soluble in ethanol(96 per cent).IDENTIFICATIONF irst identification: A, :A,B,D, Melting point ( ): 155 C to 159 To ml of solution S (see Tests) add 50 ml ofwater Rthen 10 ml of1 M sodium hydroxideand dilute ml withwater R. Examined between 250 nm and350 nm ( ), the solution shows only 1 absorptionmaximum at 284 nm. The specific absorbance at theabsorption maximum is about 50 (dried substance).

5 C. Infrared absorption spectrophotometry ( ).Preparation: dried substance prepared as a disc ofpotassium bromide :Ph. Eur. reference spectrum of acid Rand mlofferric chloride solution R2and heat on a blue colour develops. Add ml ofnitric acid changes to It gives the reaction of alkaloids ( ).TESTSS olution S. Dissolve 50 mg incarbon dioxide-free water Rand dilute to ml with the same of solution. Solution S is clear ( )andcolourless ( , Method II).Specific optical rotation( ): 142 to 146 (driedsubstance).Dissolve g inethanol (96 per cent) Rand dilute ml with the same substances.

6 Liquid chromatography ( ).Test solution. Dissolve g of the substance to beexamined and g ofsodium octanesulphonate Rin themobile phase and dilute to ml with the mobile solution (a). Dissolve mg ofcodeineimpurity A CRSin the mobile phase and dilute to mlwith the mobile solution (b). Dilute ml of reference solution (a)to ml with the mobile solution (c). ml with the mobile phase. Dilute ml of this solutionto ml with the mobile solution (d). To ml of the test solution, ml of reference solution (a).Column: size:l= , = , stationary phase:end-capped octylsilyl silica gel forchromatography R(5 m).

7 Mobile octanesulphonate Rin a mixture of 20 ml ofglacial acetic acid Rand 250 ml ofacetonitrile Rand dilute to 1000 ml withwater rate:2 : spectrophotometer at 245 :10 time: 10 times the retention time of retentionwith reference to CODEINE (retentiontime = about 6 min): impurity B = about ;impurity E = about ; impurity A = about ;impurity C = about ; impurity D = about suitability: reference solution (d): resolution: minimum 3 between the peaks due to codeineand impurity : correction factor: for the calculation of content, multiplythe peak area of impurity C by , impurity A: not more than twice the area of the principalpeak in the chromatogram obtained with referencesolution (b) ( per cent), impurities B, C, D, E:foreachimpurity,notmorethantwice the area of the principal peak in the chromatogramobtained with reference solution (c) ( per cent), any other impurity.

8 For each impurity, not more than thearea of the principal peak in the chromatogram obtainedwith reference solution (c) ( per cent), sum of impurities other than A:notmorethan10timesthe area of the principal peak in the chromatogramobtained with reference solution (c) ( per cent), disregard limit: times the area of the principal peakin the chromatogram obtained with reference solution (c)( per cent).Loss on drying( ): per cent to per cent, ash( ): maximum per cent, determinedon g in 10 ml ofanhydrous acetic acid ml ofdioxan M perchloric ml ofcrystal violet solution Ras M perchloric acidis equivalent to mgof from impurities: A, B, C, D, detectable impurities(the following substanceswould, if present at a sufficient level, be detected by oneor other of the tests in the monograph.)

9 They are limitedby the general acceptance criterion for other/unspecifiedimpurities and/or by the general monographSubstances forpharmaceutical use (2034).Itisthereforenotnecessarytoidenti fy these impurities for demonstration of Control of impurities in substances forpharmaceutical use):F, (1)applytoallmonographsandothertexts1595 CODEINE hydrochloride dihydrateEUROPEAN PHARMACOPOEIA ,R2=R3=H:7,8-didehydro-4,5 -epoxy-3,6 -dimethoxy-17-methylmorphinan (methylcodeine), ,R3=H:7,8-didehydro-4,5 -epoxy-3-methoxy-17-methylmorphinan-6 ,10-diol,F.

10 R1=R3=OH,R2=H:7,8-didehydro-4,5 -epoxy-3-methoxy-17-methylmorphinan-6 ,14-diol,B. morphine,C. 7,7 ,8,8 -tetradehydro-4,5 :4 ,5 -diepoxy-3,3 -dimethoxy-17,17 -dimethyl-2,2 -bimorphinanyl-6 ,6 -diol (codeinedimer),D. 7,8-didehydro-2-[(7,8-didehydro-4,5 -epoxy-6 -hydroxy-17-methylmorphinan-3-yl)oxy]-4, 5 -epoxy-3-methoxy-17-methylmorphinan-6 -ol (3-O-(codein-2-yl)morphine),G. 6,7,8,14-tetradehydro-4,5 -epoxy-3,6-dimethoxy-17-methylmorphinan (thebaine).01/2008:1412 CODEINE HYDROCHLORIDEDIHYDRATEC odeini hydrochloridum dihydricumC18H22 ClNO3, ,8-Didehydro-4,5 -epoxy-3-methoxy-17-methylmorphinan-6 -ol hydrochloride : per cent to per cent (anhydroussubstance).