346 Benzyl Alcohol / Official Monographs
Benzole Acid in this boiling solution, and add 0.50 mL of
0.02 mol/L potassium permanganate VS: a red color persists
for at least 15 seconds.
(4) Phthalic acid—To O . l O g of Benzole Acid add 1 mL
of water and 1 mL of resorcinol-sulfuric acid TS, and heat
the mixture in an oil bath heated at a temperature between
120°C and 125°C. After evaporating the water, heat the
residue for 90 minutes, cool, and dissolve in 5 mL of water.
To 1 mL of the solution add 10 mL of a solution of sodium
hydroxide (43 in 500), shake, then examine under light at a
wavelength between 470 nm and 490 nm: the green fluores-
cence of the solution is not more intense than that of the fol-
lowing control solution.
Control solution: Dissolve 61 mg of potassium hydrogen
phthalate in water to make exactly 1000 mL. Measure exactly
1 mL of the solution, add 1 mL of resorcinol-sulfuric acid
TS, and proceed as directed above.
(5) Readily carbonizable substances <1.15>—Perform the
test with 0.5 g of Benzoic Acid. The solution is not more
colored than Matching Fluid Q.
Loss on drying <2.41> Not more than 0.5% (1 g, silica gel,
3 hours).
Residue on ignition <2.44> Not more than 0.05% (1 g).
Assay Weigh accurately about 0.5 g of Benzoic Acid, previ-
ously dried, dissolve in 25 mL of neutralized ethanol and 25
mL of water, and titrate <2.50> with 0.1 mol/L sodium
hydroxide VS (indicator: 3 drops of phenolphthalein TS).
Each mL of 0.1 mol/L sodium hydroxide VS
= 12.21 mg of C7H6O2
Containers and storage Containers—Well-closed contain-
ers.
Benzyl Alcohol
C7H8O: 108.14
Benzyl alcohol [100-51-6]
This monograph is harmonized with the European
Pharmacopoeia and the U.S. Pharmacopeia. The parts
of the text that are not harmonized are marked with
symbols (* »).
Benzyl Alcohol contains not less than 98.0% and not
more than 100.5% of C7H8O.
*The label states, where applicable, that it is suitable
for use in the manufacture of injection forms.*
*Description Benzyl Alcohol is a clear, colorless oily liq-
uid.
It is miscible with ethanol (95), with fatty oils and with es-
sential oils.
It is soluble in water.
Specific gravity d^\ 1.043 - 1.049,
* Identification Determine the infrared absorption spec-
trum of Benzyl Alcohol as directed in the liquid film method
JP XV
under Infrared Spectrophotometry <Z25>, and compare'the
spectrum with the Reference Spectrum: both spectra exhibit
similar intensities of absorption at the same wave numbers.,
Refractive index <2.45> «5°: 1.538 - 1.541
Purity (1) Clarity and color of solution—Dissolve 2.0 mL
of Benzyl Alcohol in 60 mL of water: the solution is clear and
colorless.
(2) Acidity—To 10 mL of Benzyl Alcohol add 10 mL of
neutralized ethanol, 2 drops of phenolphthalein TS and 1.0
mL of 0.1 mol/L sodium hydroxide VS: a red color develops.
(3) Benzaldehyde and other related substances—Use Ben-
zyl Alcohol as the sample solution. Separately, weigh exactly
0.750 g of benzaldehyde and 0.500 g of cyclohexylmethanol,
and add Benzyl Alcohol to make exactly 25 mL. Pipet 1 mL
of this solution, add exactly 2 mL of ethylbenzene internal
standard solution and exactly 3 mL of dicyclohexyl internal
standard solution, then add Benzyl Alcohol to make exactly
20 mL, and use this solution as the standard solution (1). Per-
form the test with 0.1 //L each of the sample solution and
standard solution (1) as directed under Gas Chromatography
<2.02> according to the following conditions: no peaks of
ethylbenzene and dicyclohexyl appear on the chromatogram
obtained with the sample solution. When 0.1 /jL of the stan-
dard solution (1) is injected, adjust the sensitivity of the de-
tector so that the peak height of ethylbenzene is not more
than 30% of the full scale of the recorder. The peak area of
benzaldehyde obtained with the sample solution is not more
than the deference between the peak areas of benzaldehyde of
the sample solution and the standard solution (1) (0.15%),
and the peak area of cyclohexylmethanol with the sample so-
lution is not more than the deference between the peak areas
of cyclohexylmethanol of the sample solution and the stan-
dard solution (1) (0.10%). The total area of the peaks having
smaller retention time than benzyl alcohol and other than
benzaldehyde and cyclohexylmethanol obtained with the
sample solution is not more than 4 times the peak area of
ethylbenzene with the standard solution (1) (0.04%). The
total area of the peaks having larger retention time than ben-
zyl alcohol obtained with the sample solution is not more
than the peak area of dicyclohexyl with the standard solution
(1) (0.3%). For these calculations the peak areas less than
1/100 times the peak area of ethylbenzene with the standard
solution (1) are excluded.
Benzyl Alcohol labeled that it is suitable for use in the
manufacture of injection forms meets the following require-
ments.
Use Benzyl Alcohol as the sample solution. Separately,
weigh exactly 0.250 g of benzaldehyde and 0.500 g of cyclo-
hexylmethanol, and add Benzyl Alcohol to make exactly 25
mL. Pipet 1 mL of this solution, add exactly 2 mL of the
ethylbenzene internal standard solution and exactly 2 mL of
the dicyclohexyl internal standard solution, then add Benzyl
Alcohol to make exactly 20 mL, and use this solution as the
standard solution (2). Perform the test with 0.1 [iL each of
the sample solution and standard solution (2) as directed un-
der Gas Chromatography <2.02> according to the following
conditions: no peaks of ethylbenzene and dicyclohexyl ap-
pear on the chromatogram obtained with the sample solu-
tion. When 0.1 juL of the standard solution (2) is injected, ad-
just the sensitivity of the detector so that the peak height of
ethylbenzene is not more than 30% of the full scale of .the
recorder. The peak area of benzaldehyde of obtained with the
 JP XV
sample solution is not more than the difference between the
peak areas of benzaldehyde of the sample solution and the
standard solution (2) (0.05%), and the peak area of cyclohex-
ylmethanol with the sample solution is not more than the
deference between the peak areas of cyclohexylmethanol of
the sample solution and the standard solution (2) (0.10%).
The total area of the peaks having smaller retention time than
benzyl alcohol and other than benzaldehyde and cyclohex-
ylmethanol obtained with the sample solution is not more
than 2 times the peak area of ethylbenzene with the standard
solution (2) (0.02%). The total area of the peaks having larg-
er retention time than benzyl alcohol obtained with the sam-
ple solution is not more than the peak area of dicyclohexyl
with the standard solution (2) (0.2%). For these calculation
the peak areas less than 1/100 times the peak area of ethyl-
benzene with the standard solution (2) are excluded.
Ethylbenzene internal standard solution: Dissolve exactly
0.100 g of ethylbenzene in Benzyl Alcohol to make exactly 10
mL. Pipet 2 mL of this solution, and add Benzyl Alcohol to
make exactly 20 mL.
Dicyclohexyl internal standard solution: Dissolve exactly
2.000 g of dicyclohexyl in Benzyl Alcohol to make exactly 10
mL. Pipet 2 mL of this solution, and add Benzyl Alcohol to
make exactly 20 mL.
Operating conditions—
Detector: A hydrogen flame-ionization detector
Column: A fused silica column 0.32 mm in inside diameter
and 30 m in length, coated inside with polyethylene glycol 20
M for gas chromatography in 0.5 /urn thickness.
Column temperature: Raise the temperature at a rate of
5°C per minutes from 50°C to 220°C, and maintain at 220°C
for 35 minutes.
Temperature of injection port: A constant temperature of
about 200°C.
Temperature of detector: A constant temperature of about
310°C.
Carrier gas: Helium
Flow rate: Adjust the flow rate so that the retention time of
benzyl alcohol is between 24 and 28 minutes.
Split ratio: Splitless
System suitability—
System performance: When the procedure is run with the
standard solution (1) under the above operating conditions,
the relative retention times of ethylbenzene, dicyclohexyl,
benzaldehyde and cyclohexylmethanol with respect to benzyl
alcohol are about 0.28, about 0.59, about 0.68 and about
0.71, respectively, and the resolution between the peaks of
benzaldehyde and cyclohexylmethanol is not less than 3.0. In
the case of Benzyl Alcohol labeled to use for injection, pro-
ceed with the standard solution (2) instead of the standard
solution (1).
(4) Peroxide value—Dissolve 5 g of Benzyl Alcohol in
30 mL of a mixture of acetic acid (100) and chloroform (3:2)
in a 250-mL glass-stoppered conical flask. Add 0.5 mL of
potassium iodide saturated solution, shake exactly for 1
minute, add 30 mL of water, and titrate <2.50> with 0.01
mol/L sodium thiosulfate VS until the blue color of the solu-
tion disappears after addition of 10 mL of starch TS near the
end point where the solution is a pale yellow color. Perform a
blank determination in the same manner. Calculate the
amount of peroxide by the following formula: not more than
5.
Amount (mEq/kg) of peroxide = {10 x (K, - K0)l /W
Official Monographs / Benzyl Benzoate 347
Vi\ Volume (mL) of 0.01 mol/L sodium thiosulfate VS
consumed in the test
K0: Volume (mL) of 0.01 mol/L sodium thiosulfate VS
consumed in the blank
W: Amount (g) of the sample
(5) Residue on evaporation—Perform the test after con-
formation that the sample meets the requirement of the
peroxide value. Transfer 10.Og of Benzyl Alcohol to a por-
celain or quartz crucible or platinum dish, previously
weighed accurately, and heat on a hot-plate at not exceeding
200°C, taking care to avoid boiling, to evaporate to dryness.
Dry the residue on the hot-plate for 1 hour, and allow to cool
in a desiccator: not more than 5 mg.
Assay Weigh accurately about 0.9 g of Benzyl Alcohol, add
exactly 15.0 mL of a mixture of pyridine and acetic anhydride
(7:1), and heat on a water bath under a reflux condenser for
30 minutes. Cool, add 25 mL of water, and titrate <2.50> the
excess acetic acid with 1 mol/L sodium hydroxide VS (indica-
tor: 2 drops of phenolphthalein TS). Perform a blank deter-
mination.
Each mL of 1 mol/L sodium hydroxide VS
= 108.1 mg of C7H8O
*Containers and storage Containers—Tight containers.
Storage—Light-resistant.,
Benzyl Benzoate
C 14 Hi 2 O 2 : 212.24
Benzyl benzoate [120-51-4}
Benzyl Benzoate contains not less than 99.0% of
C14H1202.
Description Benzyl Benzoate is a colorless, clear, viscous
liquid. It has a faint, aromatic odor and a pungent, burning
taste.
It is miscible with ethanol (95) and with diethyl ether.
It is practically insoluble in water.
Congealing point: about 17°C
Specific gravity df0: about 1.123
Boiling point: about 323°C
Identification (1) Heat gently 1 mL of Benzyl Benzoate
with 5 mL of sodium carbonate TS and 2 mL of potassium
permanganate TS: the odor of benzaldehyde is perceptible.
(2) Warm the titrated mixture obtained in the Assay on a
water bath to remove ethanol, and add 0.5 mL of iron (III)
chloride TS: a light yellow-red precipitate is produced, which
turns white on the addition of dilute hydrochloric acid.
Refractive index <2.45> n^: 1.568 - 1.570
Purity Acidity—Dissolve S.OmL of Benzyl Benzoate in 25
mL of neutralized ethanol, and add 0.50 mL of 0.1 mol/L so-