Lidocaine Hydrochloride

(Ph. Eur. monograph 0227)

C₁₄H₂₂N₂O,HCl,H₂O    288.8    6108-05-0

Local anaesthetic; Class I antiarrhythmic.

Lidocaine Gel

Lidocaine and Chlorhexidine Gel

Lidocaine Injection

Lidocaine and Adrenaline Injection/Lidocaine and Epinephrine Injection

Sterile Lidocaine Solution

Ph Eur

2-(Diethylamino)-N-(2,6-dimethylphenyl)acetamide hydrochloride monohydrate.

99.0 per cent to 101.0 per cent (anhydrous substance).

White or almost white, crystalline powder.

Very soluble in water, freely soluble in ethanol (96 per cent).

First identification  B, D.

Second identification  A, C, D.

A. Melting point (2.2.14): 74 °C to 79 °C, determined without previous drying.

B. Infrared absorption spectrophotometry (2.2.24).

Comparison  lidocaine hydrochloride CRS.

C. To about 5 mg add 0.5 mL of fuming nitric acid R. Evaporate to dryness on a water-bath, cool and dissolve the residue in 5 mL of acetone R. Add 0.2 mL of alcoholic potassium hydroxide solution R. A green colour is produced.

D. It gives reaction (a) of chlorides (2.3.1).

Dissolve 1.0 g in carbon dioxide-free water R and dilute to 20 mL with the same solvent.

Solution S is clear (2.2.1) and colourless (2.2.2, Method II).

4.0 to 5.5.

Dilute 1 mL of solution S to 10 mL with carbon dioxide-free water R.

Liquid chromatography (2.2.29).

Test solution  Dissolve 50.0 mg of the substance to be examined in the mobile phase and dilute to 10.0 mL with the mobile phase.

Reference solution (a)  Dissolve 50.0 mg of 2,6-dimethylaniline R (impurity A) in the mobile phase and dilute to 100.0 mL with the mobile phase. Dilute 10.0 mL of this solution to 100.0 mL with the mobile phase.

Reference solution (b)  Dissolve 5 mg of 2-chloro-N-(2,6-dimethylphenyl)acetamide R (impurity H) in the mobile phase and dilute to 10 mL with the mobile phase.

Reference solution (c)  Dilute 1.0 mL of the test solution to 10.0 mL with the mobile phase.

Reference solution (d)  Mix 1.0 mL of reference solution (a), 1.0 mL of reference solution (b) and 1.0 mL of reference solution (c) and dilute to 100.0 mL with the mobile phase.

• — size: l = 0.15 m, Ø = 3.9 mm;

• — stationary phase: end-capped polar-embedded octadecylsilyl amorphous organosilica polymer R (5 µm);

• — temperature: 30 °C.

Mobile phase  Mix 30 volumes of acetonitrile for chromatography R and 70 volumes of a 4.85 g/L solution of potassium dihydrogen phosphate R adjusted to pH 8.0 with strong sodium hydroxide solution R.

Flow rate  1.0 mL/min.

Detection  Spectrophotometer at 230 nm.

Injection  20 µL.

Run time  3.5 times the retention time of lidocaine.

Relative retention  With reference to lidocaine (retention time = about 17 min): impurity H = about 0.37; impurity A = about 0.40.

System suitability  Reference solution (d):

• — resolution: minimum 1.5 between the peaks due to impurities H and A.

• — impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (d) (0.01 per cent);

• — unspecified impurities: for each impurity, not more than the area of the peak due to lidocaine in the chromatogram obtained with reference solution (d) (0.10 per cent);

• — total: not more than 5 times the area of the peak due to lidocaine in the chromatogram obtained with reference solution (d) (0.5 per cent);

• — disregard limit: 0.5 times the area of the peak due to lidocaine in the chromatogram obtained with reference solution (d) (0.05 per cent).

Maximum 5 ppm.

Dissolve 1.0 g in water R and dilute to 25 mL with the same solvent. Carry out the prefiltration. 10 mL of the prefiltrate complies with test E. Prepare the reference solution using 2 mL of lead standard solution (1 ppm Pb) R.

5.5 per cent to 7.0 per cent, determined on 0.25 g.

Maximum 0.1 per cent, determined on 1.0 g.

Dissolve 0.220 g in 50 mL of ethanol (96 per cent) R and add 5.0 mL of 0.01 M hydrochloric acid. Carry out a potentiometric titration (2.2.20), using 0.1 M sodium hydroxide. Read the volume added between the 2 points of inflexion.

1 mL of 0.1 M sodium hydroxide is equivalent to 27.08 mg of C₁₄H₂₃ClN₂O.

Protected from light.

Specified impurities  A.

Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other/unspecified impurities and/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use): B, C, D, E, F, G, H, I, J, K.

A. R = H: 2,6-dimethylaniline,

C. R = CO-CH₃: N-(2,6-dimethylphenyl)acetamide,

D. R = CO-CH₂-NH-C₂H₅: N-(2,6-dimethylphenyl)-2-(ethylamino)acetamide,

G. R = CO-CH₂-NH-CH(CH₃)₂: N-(2,6-dimethylphenyl)-2-[(1-methylethyl)amino]acetamide,

H. R = CO-CH₂-Cl: 2-chloro-N-(2,6-dimethylphenyl)acetamide,

K. R = CO-CH₂-N(CH₃)C₂H₅: N-(2,6-dimethylphenyl)-2-(ethylmethylamino)acetamide,

B. 2-(diethylazinoyl)-N-(2,6-dimethylphenyl)acetamide (lidocaine N²-oxide),

E. 2-2′-(azanediyl)bis[N-(2,6-dimethylphenyl)acetamide],

F. R1 = CH₃, R2 = R3 = H: 2-(diethylamino)-N-(2,3-dimethylphenyl)acetamide,

I. R1 = R3 = H, R2 = CH₃: 2-(diethylamino)-N-(2,4-dimethylphenyl)acetamide,

J. R1 = R2 = H, R3 = CH₃: 2-(diethylamino)-N-(2,5-dimethylphenyl)acetamide.

Ph Eur