(Ph. Eur. 11.6 update)
General Notices
(Ph. Eur. monograph 2909)
C15H24N2O2 264.4 94-24-6
Action and use
Local anaesthetic.
Ph Eur
DEFINITION
2-(Dimethylamino)ethyl 4-(butylamino)benzoate.
Content
99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder.
Solubility
Very slightly soluble in water, freely soluble in methylene chloride, soluble in ethanol (96 per cent).
mp
About 44 °C.
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison tetracaine CRS.
TESTS
Appearance of solution
The solution is clear (2.2.1) and colourless (2.2.2, Method II).
Dissolve 2.0 g in ethanol (96 per cent) R and dilute to 10 mL with the same solvent.
Related substances
Liquid chromatography (2.2.29).
Test solution Dissolve 0.100 g of the substance to be examined in acetonitrile R and dilute to 50.0 mL with the same solvent.
Reference solution (a) Dilute 1.0 mL of the test solution to 100.0 mL with acetonitrile R. Dilute 1.0 mL of this solution to 10.0 mL with acetonitrile R.
Reference solution (b) Dissolve 10 mg of 4-aminobenzoic acid R (impurity A), 10 mg of 4-(butylamino)benzoic acid R (impurity B) and 10 mg of methyl 4-(butylamino)benzoate R (impurity C) in acetonitrile R and dilute to 50 mL with the same solvent. Dilute 1 mL of the solution to 10 mL with the test solution.
Column:
— size: l = 0.15 m, Ø = 4.6 mm;
— stationary phase: end-capped octadecylsilyl amorphous organosilica polymer for chromatography R (5 μm);
— temperature: 30 °C.
Mobile phase:
— mobile phase A: dissolve 1.36 g of potassium dihydrogen phosphate R in water for chromatography R, add 0.5 mL of phosphoric acid R and dilute to 1000 mL with water for chromatography R;
— mobile phase B: acetonitrile R;
| Time (min) | Mobile phase A (per cent V/V) | Mobile phase B (per cent V/V) |
| 0 – 3 | 80 | 20 |
| 3 – 18 | 80 → 4 | 20 → 60 |
| 18 – 23 | 40 | 60 |
Flow rate 1.5 mL/min.
Detection Spectrophotometer at 300 nm.
Injection 5 μL.
Identification of impurities Use the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B and C.
Relative retention With reference to tetracaine (retention time = about 7 min): impurity A = about 0.4; impurity B = about 1.6; impurity C = about 2.2.
System suitability Reference solution (b):
— resolution: minimum 5.0 between the peaks due to tetracaine and impurity B.
Calculation of percentage contents:
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— correction factors: multiply the peak areas of the following impurities by the corresponding correction factor: impurity B = 0.7; impurity C = 0.7;
— for each impurity, use the concentration of tetracaine in reference solution (a).
Limits:
— impurities B, C: for each impurity, maximum 0.15 per cent;
— impurity A: maximum 0.05 per cent;
— unspecified impurities: for each impurity, maximum 0.10 per cent;
— total: maximum 0.3 per cent;
— reporting threshold: 0.05 per cent, except for impurity A.
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 30 °C for 2 h.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.300 g in 50 mL of a mixture of 25 volumes of water R and 75 volumes of ethanol (96 per cent) R.
Titrate with 0.1 M hydrochloric acid, determining the end-point potentiometrically (2.2.20).
1 mL of 0.1 M hydrochloric acid is equivalent to 26.44 mg of C15H24N2O2
STORAGE
In an airtight container, protected from light.
IMPURITIES
Specified impurities A, B, C.
A. 4-aminobenzoic acid,
B. 4-(butylamino)benzoic acid,
C. methyl 4-(butylamino)benzoate
