EUROPEAN PHARMACOPOEIA 11.

0 Menthol, racemic

Sulfated ash (2.4.14). Not more than 0.1 per cent, determined C. Examine the chromatograms obtained in the test for
on 1.0 g. related substances.
ASSAY Results : the principal peak in the chromatogram obtained
with test solution (b) is similar in position and approximate
Dissolve 0.150 g in 15 mL of glacial acetic acid R in a flask with dimensions to the principal peak in the chromatogram
a stopper fitted with a valve. Add 15 mL of dilute hydrochloric obtained with reference solution (c).
acid R and 1 g of zinc powder R. Close the flask. Allow the
mixture to stand for 60 min, protected from light, with D. Dissolve 0.20 g in 0.5 mL of anhydrous pyridine R. Add
occasional shaking. Filter the solution over a cotton wad, wash 3 mL of a 150 g/L solution of dinitrobenzoyl chloride R in
with three quantities, each of 10 mL, of carbon dioxide-free anhydrous pyridine R. Heat on a water-bath for 10 min.
water R. Add 0.1 mL of ferroin R and immediately titrate the Add 7.0 mL of water R in small quantities with stirring
combined filtrate and washings with 0.1 M ammonium and and allow to stand in iced water for 30 min. A precipitate
cerium nitrate. is formed. Allow to stand and decant the supernatant.
Wash the precipitate with 2 quantities, each of 5 mL, of iced
1 mL of 0.1 M ammonium and cerium nitrate is equivalent
water R, recrystallise from 10 mL of acetone R, wash with
to 8.61 mg of C11H8O2.
iced acetone R and dry at 75 °C at a pressure not exceeding
STORAGE 2.7 kPa for 30 min. The crystals melt (2.2.14) at 130 °C to
Store protected from light. 131 °C.
TESTS
01/2008:0623
corrected 7.0 Solution S. Dissolve 2.50 g in 10 mL of ethanol (96 per cent) R
and dilute to 25.0 mL with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and
colourless (2.2.2, Method II).
Acidity or alkalinity. Dissolve 1.0 g in ethanol (96 per cent) R
MENTHOL, RACEMIC and dilute to 10 mL with the same solvent. Add 0.1 mL of
phenolphthalein solution R. The solution is colourless. Not
Mentholum racemicum more than 0.5 mL of 0.01 M sodium hydroxide is required to
change the colour of the indicator to pink.
Optical rotation (2.2.7) : − 0.2° to + 0.2°, determined on
solution S.
Related substances. Gas chromatography (2.2.28).
Test solution (a). Dissolve 0.20 g of the substance to be
C10H20O Mr 156.3 examined in methylene chloride R and dilute to 50.0 mL with
[89-78-1] the same solvent.
Test solution (b). Dilute 1.0 mL of test solution (a) to 10.0 mL
DEFINITION with methylene chloride R.
Mixture of equal parts of (1RS,2SR,5RS)-5-methyl-2-(1-
Reference solution (a). Dissolve 40.0 mg of the substance to be
methylethyl)cyclohexanol.
examined and 40.0 mg of isomenthol R in methylene chloride R
CHARACTERS and dilute to 100.0 mL with the same solvent.
Appearance : free-flowing or agglomerated, crystalline powder Reference solution (b). Dilute 0.10 mL of test solution (a) to
or prismatic or acicular, colourless, shiny crystals. 100.0 mL with methylene chloride R.
Solubility : practically insoluble in water, very soluble in Reference solution (c). Dissolve 40.0 mg of menthol CRS in
ethanol (96 per cent) and in light petroleum, freely soluble in methylene chloride R and dilute to 100.0 mL with the same
fatty oils and in liquid paraffin, very slightly soluble in glycerol. solvent.
mp : about 34 °C. Column :
IDENTIFICATION – material : glass ;
First identification : A, C. – size : l = 2.0 m, Ø = 2 mm ;
Second identification : B, D. – stationary phase : diatomaceous earth for gas
A. Optical rotation (see Tests). chromatography R impregnated with 15 per cent m/m of
macrogol 1500 R.
B. Thin-layer chromatography (2.2.27).
Carrier gas : nitrogen for chromatography R.
Test solution. Dissolve 25 mg of the substance to be
examined in methanol R and dilute to 5 mL with the same Flow rate : 30 mL/min.
solvent. Temperature :
Reference solution. Dissolve 25 mg of menthol CRS in – column : 120 °C ;
methanol R and dilute to 5 mL with the same solvent. – injection port : 150 °C ;
Plate : TLC silica gel G plate R.
– detector : 200 °C.
Mobile phase : ethyl acetate R, toluene R (5:95 V/V).
Detection : flame ionisation.
Application : 2 μL.
Injection : 1 μL.
Development : over a path of 15 cm.
Drying : in air, until the solvents have evaporated. Run time : twice the retention time of menthol.
Detection : spray with anisaldehyde solution R and heat at System suitability :
100-105 °C for 5-10 min. – resolution : minimum 1.4 between the peaks due to menthol
Results : the principal spot in the chromatogram obtained and isomenthol in the chromatogram obtained with
with the test solution is similar in position, colour and size reference solution (a);
to the principal spot in the chromatogram obtained with – signal-to-noise ratio : minimum 5 for the principal peak in
the reference solution. the chromatogram obtained with reference solution (b).

General Notices (1) apply to all monographs and other texts 3343
Mepivacaine hydrochloride EUROPEAN PHARMACOPOEIA 11.0

Limits : test solution (a) : Detection : examine in ultraviolet light at 254 nm.
– total : not more than 1 per cent of the area of the principal System suitability : reference solution (b) :
peak ; – the chromatogram shows 2 clearly separated principal
– disregard limit : 0.05 per cent of the area of the principal spots.
peak. Results : the principal spot in the chromatogram obtained
Residue on evaporation : maximum 0.05 per cent. with the test solution is similar in position and size to
Evaporate 2.00 g on a water-bath and heat in an oven at the principal spot in the chromatogram obtained with
100-105 °C for 1 h. The residue weighs not more than 1.0 mg. reference solution (a).
C. It gives reaction (a) of chlorides (2.3.1).

01/2019:1242 TESTS
corrected 10.0 Solution S. Dissolve 1.500 g in carbon dioxide-free water R
and dilute to 30.0 mL with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and not
more intensely coloured than reference solution B7 (2.2.2,
Method II).
MEPIVACAINE HYDROCHLORIDE pH (2.2.3) : 4.0 to 5.0.
Dilute 2 mL of solution S to 5 mL with carbon dioxide-free
Mepivacaini hydrochloridum water R.
Optical rotation (2.2.7) : − 0.10° to + 0.10°, determined on
solution S.
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 20.0 mg of the substance to be
examined in the mobile phase and dilute to 10.0 mL with the
mobile phase.
C15H23ClN2O Mr 282.8
[1722-62-9] Reference solution (a). Dissolve 20.0 mg of the substance to be
examined and 30.0 mg of mepivacaine impurity B CRS in the
DEFINITION mobile phase and dilute to 100.0 mL with the mobile phase.
(2RS)-N-(2,6-Dimethylphenyl)-1-methylpiperidine-2- Dilute 1.0 mL of the solution to 100.0 mL with the mobile
carboxamide hydrochloride. phase.
Content : 98.5 per cent to 101.0 per cent (dried substance). Reference solution (b). Dilute 1.0 mL of the test solution to
100.0 mL with the mobile phase. Dilute 1.0 mL of this solution
CHARACTERS to 10.0 mL with the mobile phase.
Appearance : white or almost white, crystalline powder. Column :
Solubility : freely soluble in water and in ethanol (96 per cent), – size : l = 0.125 m, Ø = 4.6 mm ;
very slightly soluble in methylene chloride. – stationary phase : base-deactivated end-capped octadecylsilyl
mp : about 260 °C, with decomposition. silica gel for chromatography R (5 μm).
It shows polymorphism (5.9). Mobile phase : mix 35 volumes of acetonitrile R1 and
65 volumes of a 2.25 g/L solution of phosphoric acid R,
IDENTIFICATION previously adjusted to pH 7.6 with strong sodium hydroxide
First identification : A, C. solution R.
Second identification : B, C. Flow rate : 1 mL/min.
A. Infrared absorption spectrophotometry (2.2.24). Detection : spectrophotometer at 220 nm.
Comparison : mepivacaine hydrochloride CRS. Injection : 20 μL.
If the spectra obtained in the solid state show differences, Run time : 3 times the retention time of mepivacaine.
dissolve the substance to be examined and the reference Identification of impurities: use the chromatogram obtained
substance separately in methanol R, evaporate to dryness with reference solution (a) to identify the peak due to
and dry in an oven at 80 °C for 45 min. Record new spectra impurity B.
using the residues. Relative retention with reference to mepivacaine (retention
B. Thin-layer chromatography (2.2.27). time = about 7 min) : impurity B = about 0.5.
Test solution. Dissolve 20 mg of the substance to be System suitability : reference solution (a) :
examined in ethanol (96 per cent) R and dilute to 5 mL with – resolution : minimum 2.5 between the peaks due to
the same solvent. impurity B and mepivacaine.
Reference solution (a). Dissolve 20 mg of mepivacaine Limits :
hydrochloride CRS in ethanol (96 per cent) R and dilute to – unspecified impurities : for each impurity, not more than the
5 mL with the same solvent. area of the principal peak in the chromatogram obtained
Reference solution (b). Dissolve 20 mg of mepivacaine with reference solution (b) (0.10 per cent) ;
hydrochloride CRS and 20 mg of lidocaine – total : not more than 5 times the area of the principal peak
hydrochloride CRS in ethanol (96 per cent) R and in the chromatogram obtained with reference solution (b)
dilute to 5 mL with the same solvent. (0.5 per cent);
Plate : TLC silica gel F254 plate R. – disregard limit : 0.5 times the area of the principal peak in
Mobile phase : concentrated ammonia R, methanol R, the chromatogram obtained with reference solution (b)
1,1-dimethylethyl methyl ether R (1:5:100 V/V/V). (0.05 per cent).
Application : 10 μL. Impurity A. Head-space gas chromatography (2.2.28).
Development : over 2/3 of the plate. Test solution. Introduce 60.0 mg of the substance to be
Drying : in air. examined into a 20 mL vial. Add 2.0 mL of a 103.0 g/L solution

3344 See the information section on general monographs (cover pages)