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Benzyl Alcohol
C7H8O 108.14
Benzenemethanol.
Benzyl alcohol [100-51-6].
»Benzyl Alcohol contains not less than 98.0percent and not more than 100.5percent of C7H8O.
Labeling— Where Benzyl Alcohol is intended for use in the manufacture of injectable dosage forms,it is so labeled.
Clarity of solution— [NOTE—The Test solutionis to be compared to Reference suspension 1in diffused daylight 5minutes after preparation of Reference suspension 1.]
Hydrazine solution— Transfer 1.0g of hydrazine sulfate to a 100-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.Allow to stand 4to 6hours before use.
Methenamine solution— Transfer 2.5g of methenamine to a 100-mLglass-stoppered flask,add 25.0mLof water,insert the glass stopper,and mix to dissolve.
Primary opalescent suspension— [NOTE—This suspension is stable for 2months,provided it is stored in a glass container free from surface defects.The suspension must not adhere to the glass and must be well mixed before use.]Transfer 25.0mLof Hydrazine solutionto the Methenamine solutionin the 100-mLglass-stoppered flask.Mix,and allow to stand for 24hours.
Opalescence standard— [NOTE—This suspension should not be used beyond 24hours after preparation.]Transfer 15.0mLof the Primary opalescent suspensionto a 1000-mLvolumetric flask,dilute with water to volume,and mix.
Reference suspensions— Transfer 5.0mLof the Opalescence standardto a 100-mLvolumetric flask,dilute with water to volume,and mix to obtain Reference suspension 1.Transfer 10.0mLof the Opalescence standardto a second 100-mLvolumetric flask,dilute with water to volume,and mix to obtain Reference suspension 2.
Test solution— Dissolve 2.0g of Benzyl Alcohol in 60mLof water,and mix.
Procedure— Transfer a sufficient portion of the Test solutionto a test tube of colorless,transparent,neutral glass with a flat base and an internal diameter of 15mm to 25mm,to obtain a depth of 40mm.Similarly transfer portions of Reference suspension 1,Reference suspension 2,and water to separate matching test tubes.Compare the Test solution,Reference suspension 1,Reference suspension 2,and water in diffused daylight,viewing vertically against a black background (see Visual Comparisonunder Spectrophotometry and Light-Scattering á851ñ).[NOTE—The diffusion of light must be such that Reference suspension 1can readily be distinguished from water,and that Reference suspension 2can readily be distinguished from Reference suspension 1.]The Test solutionshows the same clarity as that of water,or its opalescence is not more pronounced than that of Reference suspension 1.
Color of solution—
Test solution— Use the Test solutionprepared in the test for Clarity of solution.
Procedure— Transfer a sufficient portion of the Test solutionto a test tube of colorless,transparent,neutral glass with a flat base and an internal diameter of 15mm to 25mm,to obtain a depth of 40mm.Similarly transfer a portion of water to a separate matching test tube.Compare the color of the Test solutionwith that of water in diffused daylight,viewing vertically against a white background (see Visual Comparisonunder Spectrophotometry and Light-Scattering á851ñ).The Test solutionhas the color of water.
Identification— Infrared Absorption á197Fñ,on undried specimen.
Peroxide value á401ñ: not more than 5.
Refractive index á831ñ: between 1.538and 1.541at 20.
Acidity— Neutralize 50mLof alcohol containing 1mLof phenolphthalein TSwith 0.10Nsodium hydroxide.Dissolve 10mLof Benzyl Alcohol in 10mLof the neutralized alcohol,and titrate with 0.10Nsodium hydroxide to the first appearance of a pink color that persists for not less than 30seconds:not more than 1.0mLis consumed.
Limit of nonvolatile residue— [NOTE—Ensure that the Benzyl Alcohol to be examined complies with the test for Peroxide value á401ñbefore performing this test.]Evaporate 10.0g of Benzyl Alcohol on a water bath to dryness,and dry the residue at 105for 1hour.Cool in a desiccator,and weigh.The residue weighs not more than 5mg:not more than 0.05%of nonvolatile residue is found.
Related compounds—
Test solution— Use the Benzyl Alcohol specimen under examination.
Ethylbenzene solution— Transfer 100mg of ethylbenzene,accurately weighed,to a 10-mLvolumetric flask,dissolve in and dilute with Test solutionto volume,and mix.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,dilute with Test solutionto volume,and mix.
Dicyclohexyl solution— Transfer 2.0g of dicyclohexyl to a 10-mLvolumetric flask,dissolve in and dilute with Test solutionto volume,and mix.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,dilute with Test solutionto volume,and mix.
Standard solution 1— Transfer 750mg of benzaldehyde,accurately weighed,and 500mg of cyclohexylmethanol,accurately weighed,to a 25-mLvolumetric flask,dissolve in and dilute with Test solutionto volume,and mix.Transfer 0.5mLof this solution to a 10-mLvolumetric flask,add 1.0mLof Ethylbenzene solutionand 1.5mLof Dicyclohexyl solution,dilute with Test solutionto volume,and mix.
Standard solution 2(where the Benzyl Alcohol under test is intended for use in the manufacture of injectable dosage forms)— Transfer about 250mg of benzaldehyde,accurately weighed,and about 500mg of cyclohexylmethanol,accurately weighed,to a 25-mLvolumetric flask,dissolve in and dilute with Test solutionto volume,and mix.Transfer 0.5mLof this solution to a 10-mLvolumetric flask,add 1.0mLof Ethylbenzene solutionand 1.0mLof Dicyclohexyl solution,dilute with Test solutionto volume,and mix.
Chromatographic system (see Chromatography á621ñ)— The gas chromatograph is equipped with a flame-ionization detector and a 0.32-mm ×30-m column coated with a 0.5-µm film of G16.Helium is used as the carrier gas flowing at a rate of 1.2mLper minute at 50.The injection port and detector temperatures are maintained at about 200and 310,respectively.The column temperature is programmed to increase linearly from 50to 220at a rate of 5per minute,and is maintained at 220for 35minutes.Chromatograph the appropriate Standard solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.28for ethylbenzene,0.59for dicyclohexyl,0.68for benzaldehyde,0.71for cyclohexylmethanol,and 1.0for benzyl alcohol;and the resolution,R,between benzaldehyde and cyclohexylmethanol is not less than 3.0.
Procedure— Separately inject equal volumes (about 0.1µL)of the appropriate Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.[NOTE—Disregard any peak having an area less than 0.01times the area of the ethylbenzene peak in the chromatogram of the appropriate Standard solution.In the chromatogram of the Test solution,verify that there are no peaks with the same retention times as those of ethylbenzene or dicyclohexyl.]
In the chromatogram of the Test solution,the area of any peak corresponding to benzaldehyde is not greater than the difference between the area of the peak due to benzaldehyde in the chromatogram of Standard solution 1(0.15%)or in the chromatogram of Standard solution 2(0.05%)and the area of the peak due to benzaldehyde in the chromatogram of the Test solution.
In the chromatogram of the Test solution,the area of any peak corresponding to cyclohexylmethanol is not greater than the difference between the area of the peak due to cyclohexylmethanol in the chromatogram of Standard solution 1(0.10%)or in the chromatogram of Standard solution 2(0.10%)and the area of the peak due to cyclohexylmethanol in the chromatogram of the Test solution.
In the chromatogram of the Test solution,the sum of the areas of any peaks with retention times less than that of benzyl alcohol,excluding the peaks due to benzaldehyde and cyclohexylmethanol,is not greater than four times the area of the ethylbenzene peak in the chromatogram of Standard solution 1(0.04%)or is not greater than two times the area of the ethylbenzene peak in the chromatogram of Standard solution 2(0.02%).
In the chromatogram of the Test solution,the sum of the areas of any peaks with retention times greater than that of benzyl alcohol is not greater than the area of the dicyclohexyl peak in the chromatogram of Standard solution 1(0.3%)or in the chromatogram of Standard solution 2(0.2%).
Assay— To about 900mg of Benzyl Alcohol,accurately weighed,add 15.0mLof a freshly prepared mixture of pyridine and acetic anhydride (7:1),and boil under reflux for 30minutes.Cool,add 25mLof water,add 0.25mLof a phenolphthalein solution prepared by dissolving 100mg of phenolphthalein in 80mLof alcohol and diluting with water to 100mL,and titrate with 1Nsodium hydroxide VS.Perform a blank determination (see Titrimetry á541ñ).Calculate the percentage of C7H8Otaken by the formula:
10.81N(VB-VU)/W,
in which VUand VBare the number of mLof 1Nsodium hydroxide used for the Benzyl Alcohol and the blank,respectively;andWis the weight,in g,of Benzyl Alcohol taken.NF23
Auxiliary Information— Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 2965
Pharmacopeial Forum:Volume No.30(2)Page 690
Phone Number:1-301-816-8323