Propylene glycol EUROPEAN PHARMACOPOEIA 7.

Mobile phase : glacial acetic acid R, water R, methanol R — unspecified impurities : for each impurity, not more than the
(1:30:70 V/V/V). area of the principal peak in the chromatogram obtained
Application : 2 μL of test solution (b) and reference with reference solution (c) (0.5 per cent) ;
solutions (a) and (b). — total : not more than twice the area of the principal peak
Development : over 2/3 of the plate. in the chromatogram obtained with reference solution (c)
Drying : in air. (1.0 per cent) ;
Detection : examine in ultraviolet light at 254 nm. — disregard limit : 0.2 times the area of the principal peak
in the chromatogram obtained with reference solution (c)
System suitability : reference solution (b) : (0.1 per cent).
— the chromatogram shows 2 clearly separated principal
spots. Sulfated ash (2.4.14): maximum 0.1 per cent, determined on
1.0 g.
Results : the principal spot in the chromatogram obtained
with test solution (b) is similar in position and size to the ASSAY
principal spot in the chromatogram obtained with reference Liquid chromatography (2.2.29) as described in the test for
solution (a). related substances with the following modification.
TESTS Injection : test solution and reference solution (b).
Solution S. Dissolve 1.0 g in ethanol (96 per cent) R and dilute Calculate the percentage content of C10H12O3 from the declared
to 10 mL with the same solvent. content of propyl parahydroxybenzoate CRS.
Appearance of solution. Solution S is clear (2.2.1) and not IMPURITIES
more intensely coloured than reference solution BY6 (2.2.2, Specified impurities : A.
Method II).
Other detectable impurities (the following substances would,
Acidity. To 2 mL of solution S add 3 mL of ethanol (96 per if present at a sufficient level, be detected by one or other of
cent) R, 5 mL of carbon dioxide-free water R and 0.1 mL of the tests in the monograph. They are limited by the general
bromocresol green solution R. Not more than 0.1 mL of 0.1 M acceptance criterion for other/unspecified impurities and/or
sodium hydroxide is required to change the colour of the by the general monograph Substances for pharmaceutical use
indicator to blue. (2034). It is therefore not necessary to identify these impurities
Related substances. Liquid chromatography (2.2.29). for demonstration of compliance. See also 5.10. Control of
Test solution. Dissolve 50.0 mg of the substance to be examined impurities in substances for pharmaceutical use) : B, C, D.
in 2.5 mL of methanol R and dilute to 50.0 mL with the mobile
phase. Dilute 10.0 mL of this solution to 100.0 mL with the
mobile phase.
Reference solution (a). Dissolve 5 mg of 4-hydroxybenzoic A. 4-hydroxybenzoic acid,
acid R (impurity A), 5 mg of ethyl parahydroxybenzoate R
(impurity C) and 5 mg of the substance to be examined in the
mobile phase and dilute to 100.0 mL with the mobile phase.
Dilute 1.0 mL of this solution to 10.0 mL with the mobile phase.
Reference solution (b). Dissolve 50.0 mg of propyl
parahydroxybenzoate CRS in 2.5 mL of methanol R and dilute B. methyl 4-hydroxybenzoate (methyl parahydroxybenzoate),
to 50.0 mL with the mobile phase. Dilute 10.0 mL of this
solution to 100.0 mL with the mobile phase.
Reference solution (c). Dilute 1.0 mL of the test solution to
20.0 mL with the mobile phase. Dilute 1.0 mL of this solution
to 10.0 mL with the mobile phase.
Column: C. ethyl 4-hydroxybenzoate (ethyl parahydroxybenzoate),
— size : l = 0.15 m, Ø = 4.6 mm ;
— stationary phase : end-capped octadecylsilyl silica gel for
chromatography R (5 μm).
Mobile phase : 6.8 g/L solution of potassium dihydrogen
phosphate R, methanol R (35:65 V/V).
D. butyl 4-hydroxybenzoate (butyl parahydroxybenzoate).
Flow rate: 1.3 mL/min.
Detection : spectrophotometer at 272 nm.
01/2008:0430
Injection : 10 μL of the test solution and reference solutions (a)
and (c).
Run time : 2.5 times the retention time of propyl
PROPYLENE GLYCOL
parahydroxybenzoate.
Relative retention with reference to propyl parahydroxybenzoate
Propylenglycolum
(retention time = about 4.5 min) : impurity A = about 0.3 ;
impurity C = about 0.7.
System suitability : reference solution (a) :
— resolution : minimum 3.0 between the peaks due to C3H8O2 Mr 76.1
impurity C and propyl parahydroxybenzoate. [57-55-6]
Limits : DEFINITION
— correction factor : for the calculation of content, multiply the Propylene glycol is (RS)-propane-1,2-diol.
peak area of impurity A by 1.4 ;
— impurity A : not more than the area of the principal peak CHARACTERS
in the chromatogram obtained with reference solution (c) A viscous, clear, colourless, hygroscopic liquid, miscible with
(0.5 per cent) ; water and with ethanol (96 per cent).

2814 See the information section on general monographs (cover pages)

IDENTIFICATION TESTS
A. Relative density (see Tests). Appearance. The substance to be examined is clear (2.2.1) and
B. Refractive index (see Tests). not more intensely coloured than reference solution BY6 (2.2.2,
C. Boiling point (2.2.12) : 184 °C to 189 °C. Method II).
D. To 0.5 mL add 5 mL of pyridine R and 2 g of finely ground Acid value (2.5.1) : maximum 0.2.
nitrobenzoyl chloride R. Boil for 1 min and pour into 15 mL Hydroxyl value (2.5.3, Method A) : maximum 10.
of cold water R with shaking. Filter, wash the precipitate
with 20 mL of a saturated solution of sodium hydrogen Iodine value (2.5.4) : maximum 1.0.
carbonate R and then with water R and dry. Dissolve in Peroxide value (2.5.5, Method A) : maximum 1.0.
boiling ethanol (80 per cent V/V) R and filter the hot Saponification value (2.5.6) : 320 to 340.
solution. On cooling, crystals are formed which, after drying
at 100-105 °C, melt (2.2.14) at 121 °C to 128 °C. Unsaponifiable matter (2.5.7): maximum 0.3 per cent,
determined on 5.0 g.
TESTS Alkaline impurities. Dissolve 2.00 g of the substance to be
Appearance. It is clear (2.2.1) and colourless (2.2.2, Method II). examined in a mixture of 1.5 mL of ethanol (96 per cent) R
Relative density (2.2.5) : 1.035 to 1.040. and 3.0 mL of ether R. Add 0.05 mL of bromophenol blue
solution R. Not more than 0.15 mL of 0.01 M hydrochloric acid
Refractive index (2.2.6) : 1.431 to 1.433. is required to change the colour of the indicator to yellow.
Acidity. To 10 mL add 40 mL of water R and 0.1 mL of Composition of fatty acids. Gas chromatography (2.4.22,
bromothymol blue solution R1. The solution is greenish-yellow. Method C). Prepare reference solution (a) as indicated in
Not more than 0.05 mL of 0.1 M sodium hydroxide is required Table 2.4.22.-2.
to change the colour of the indicator to blue.
Column :
Oxidising substances. To 10 mL add 5 mL of water R, 2 mL of — material : fused silica,
potassium iodide solution R and 2 mL of dilute sulfuric acid R
and allow to stand in a ground-glass-stoppered flask protected — size : l = 30 m, Ø = 0.32 mm,
from light for 15 min. Titrate with 0.05 M sodium thiosulfate, — stationary phase: macrogol 20 000 R (film thickness
using 1 mL of starch solution R as indicator. Not more than 0.5 μm),
0.2 mL of 0.05 M sodium thiosulfate is required. Carrier gas : helium for chromatography R.
Reducing substances. To 1 mL add 1 mL of dilute ammonia R1 Flow rate : 1.3 mL/min.
and heat in a water-bath at 60 °C for 5 min. The solution is Split ratio : 1 :100.
not yellow. Immediately add 0.15 mL of 0.1 M silver nitrate
and allow to stand for 5 min. The solution does not change its Temperature :
appearance. Time Temperature
Heavy metals (2.4.8). Mix 4 mL with 16 mL of water R. 12 mL of (min) (°C)
the solution complies with test A for heavy metals (5 ppm m/V). Column 0-1 70
Prepare the reference solution using lead standard solution 1 - 35 70 → 240
(1 ppm Pb) R.
35 - 50 240
Water (2.5.12). Not more than 0.2 per cent, determined on
5.00 g by the semi-micro determination of water. Injection port 250
Sulfated ash (2.4.14). Heat 50 g until it burns and ignite. Allow Detector 250
to cool. Moisten the residue with sulfuric acid R and ignite ;
repeat the operations. The residue weighs not more than 5 mg Detection : flame ionisation.
(0.01 per cent). Composition of the fatty acid fraction of the substance to be
STORAGE examined :
Store in an airtight container. — caproic acid : maximum 2.0 per cent,
— caprylic acid : 50.0 per cent to 80.0 per cent,
01/2008:2122 — capric acid : 20.0 per cent to 50.0 per cent,
— lauric acid : maximum 3.0 per cent,
PROPYLENE GLYCOL — myristic acid : maximum 1.0 per cent.
DICAPRYLOCAPRATE Water (2.5.12) : maximum 0.1 per cent, determined on 5.00 g.
Total ash (2.4.16) : maximum 0.1 per cent, determined on 2.0 g.
Propylenglycoli dicaprylocapras STORAGE
DEFINITION Protected from light.
Propylene glycol diesters of saturated fatty acids, mainly caprylic
(octanoic) acid and capric (decanoic) acid, of vegetable origin.
01/2008:2087
CHARACTERS
Appearance : almost colourless to light yellow, oily liquid. PROPYLENE GLYCOL DILAURATE
Solubility : practically insoluble in water, soluble in fatty oils
and in light petroleum, slightly soluble in anhydrous ethanol. Propylenglycoli dilauras
IDENTIFICATION DEFINITION
A. Refractive index (2.2.6) : 1.439 to 1.442. Mixture of propylene glycol mono- and diesters of lauric
B. Relative density (2.2.5) : 0.910 to 0.930. (dodecanoic) acid.
C. Viscosity (2.2.9) : 9 mPa·s to 12 mPa·s. Content : minimum 70.0 per cent of diesters and maximum
D. Composition of fatty acids (see Tests). 30.0 per cent of monoesters.

General Notices (1) apply to all monographs and other texts 2815