The British Pharmacopoeia 2003

Sterile Lidocaine Solution

General Notices
NOTE : The name Sterile Lignocaine Solution was formerly used in the United Kingdom.

Definition

Sterile Lidocaine Solution is a sterile cutaneous solution. It contains Lidocaine Hydrochloride in

Purified Water.

The solution complies with the requirements stated under Liquids for Cutaneous Application and with
the following requirements.

Content of lidocaine hydrochloride, C 14H22N2O,HCl,H2O

95.0 to 105.0% of the stated amount.

Identification

A. Make a volume containing 0.1 g of Lidocaine Hydrochloride alkaline with 5M sodium hydroxide,
filter, wash the residue with water , dissolve it in 1 ml of ethanol (96%), add 0.5 ml of a 10% w/v
solution of cobalt(II) chloride and shake for 2 minutes. A bluish-green precipitate is produced.

B. To a volume containing 0.1 g of Lidocaine Hydrochloride add 10 ml of picric acid solution R1.
The melting point of the precipitate, after washing with water and drying at 105, is about 229,
Appendix V A.

C. Yields the reactions characteristic of chlorides, Appendix VI.

2,6-Dimethylaniline

Dilute the solution to contain 0.25% w/v of Lidocaine Hydrochloride. To 10 ml of this solution add 2M
sodium hydroxide until the solution is just alkaline and extract with three 5 ml quantities of
chloroform, dry the combined chloroform extracts over anhydrous sodium sulphate, filter, wash with
a further 5 ml of chloroform and evaporate the filtrate to dryness at a pressure of 2 kPa. Dissolve the
residue in 2 ml of methanol , add 1 ml of a 1% w/v solution of 4-dimethylaminobenzaldehyde in
methanol and 2 ml of glacial acetic acid and allow to stand at room temperature for 10 minutes. Any
yellow colour produced is not more intense than the colour obtained by repeating the operation using
10 ml of a solution of 2,6-dimethylaniline in water containing 1 g per ml in place of the solution
being examined (400 ppm).

Assay

Make a quantity containing 0.1 g of Lidocaine Hydrochloride alkaline with 2M sodium hydroxide and
extract with three 20 ml quantities of chloroform, washing each extract with the same 10 ml of water .
Filter the washed extracts through a filter paper moistened with chloroform and wash the filter with
10 ml of chloroform. Add the washings to the filtrate and carry out Method I for non-aqueous titration,
Appendix VIII A, using 0.02M perchloric acid VS as titrant and crystal violet solution as indicator.
Each ml of 0.02 M perchloric acid VS is equivalent to 5.776 mg of C14H22N2O,HCl,H2O.

Sterility

Complies with the test for sterility, Appendix XVI A.

Labelling

The label states (1) that the solution is not intended for injection; (2) that the solution should be used

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on one occasion only and that any remainder should be discarded; (3) the date after which the
solution is not intended to be used; (4) the conditions under which it should be stored.

The label indicates the pharmaceutical form as 'cutaneous solution'.

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Appendix VI Qualitative reactions and tests

(Ph. Eur. method 2.3.1)Acetates

A. Heat the substance being examined with an equal quantity of oxalic acid. Acidic vapours with the
characteristic odour of acetic acid are evolved.

B. To about 30 mg of the substance being examined dissolved in 3 ml of water or to 3 ml of the

prescribed solution add successively 0.25 ml of lanthanum nitrate solution, 0.1 ml of 0.05M iodine
and 0.05 ml of 2M ammonia and heat the mixture carefully to boiling. After a few minutes a blue
precipitate or a dark blue colour is produced.

Acetyl groups

In a test tube (about 180 mm 18 mm) place about 15 mg of the substance being examined or the
prescribed quantity and 0.15 ml of orthophosphoric acid. Close the tube with a stopper through
which passes a small test tube (about 100 mm 10 mm) containing water to act as a condenser.
Hang a drop of lanthanum nitrate solution on the outside of the smaller tube.

Except for substances hydrolysable only with difficulty, place the apparatus in a water bath for 5
minutes and remove the smaller tube. Mix the drop with 0.05 ml of 0.01M iodine on a tile and add, at
the edge, 0.05 ml of 2M ammonia. After 1 or 2 minutes a blue colour is produced at the junction of
the two drops which intensifies and persists for a short time.

For substances hydrolysable only with difficulty, proceed as described above but heat the mixture
slowly to boiling point over an open flame instead of using a water bath.

Alkaloids

Dissolve a few mg or the prescribed quantity of the substance being examined in 5 ml of water ,
acidify with 2M hydrochloric acid and add 1 ml of potassium iodobismuthate solution. An orange or
orange-red precipitate is produced immediately.

Aluminium salts

To about 15 mg of the substance being examined dissolved in 2 ml of water or to 2 ml of the

prescribed solution add about 0.5 ml of 2M hydrochloric acid and about 0.5 ml of thioacetamide
reagent; no precipitate is produced. Add 2M sodium hydroxide dropwise; a gelatinous white
precipitate is produced which dissolves on further addition of 2 M sodium hydroxide. Gradually add
ammonium chloride solution; the gelatinous white precipitate reappears.

Amines, primary aromatic

Acidify the prescribed solution with 2M hydrochloric acid or dissolve 0.1 g in 2 ml of 2M hydrochloric
acid and add 0.2 ml of sodium nitrite solution. After 1 to 2 minutes add the solution to 1 ml of 2-
naphthol solution. An intense orange or red colour and, usually, a precipitate of the same colour are
produced.

Ammonium salts

To the prescribed solution add 0.2 g of magnesium oxide. Pass a current of air through the mixture
and direct the gas that escapes just beneath the surface of a mixture of 1 ml of 0.1M hydrochloric
acid and 0.05 ml of methyl red solution; the colour of the solution changes to yellow. Add 1 ml of a
freshly prepared 10% w/v solution of sodium cobaltinitrite; a yellow precipitate is produced.

Ammonium salts and salts of volatile bases

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hydrochloric acid.

Chlorides

A. Dissolve a quantity of the substance being examined containing about 2 mg of chloride ion in 2 ml
of water or use 2 ml of the prescribed solution. Acidify with 2M nitric acid, add 0.4 ml of silver nitrate
solution R1, shake and allow to stand; a curdy, white precipitate is produced. Centrifuge and wash
the precipitate with three 1-ml quantities of water . Carry out this operation rapidly in subdued light,
disregarding the fact that the supernatant solution may not become perfectly clear . Suspend the
precipitate in 2 ml of water and add 1.5 ml of 10M ammonia; the precipitate dissolves easily with the
possible exception of a few large particles which dissolve slowly.

B. Introduce into a test tube a quantity of the substance being examined containing about 15 mg of
chloride ion or the prescribed quantity, add 0.2 g of potassium dichromate and 1 ml of sulphuric acid
and place a filter paper strip moistened with 0.1 ml of diphenylcarbazide solution over the opening of
the test tube. The paper turns violet-red. The moistened paper must not come into contact with the
potassium dichromate solution.

Citrates

For monographs of the European Pharmacopoeia, use test A only.

A. To a quantity of the substance being examined corresponding to about 50 mg of citric acid

dissolved in 5 ml of water or to 5 ml of the prescribed solution add 0.5 ml of sulphuric acid and 1 ml
of potassium permanganate solution and warm until the colour of the permanganate is discharged.
Add 0.5 ml of a 10% w/v solution of sodium nitroprusside in 1M sulphuric acid and 4 g of sulphamic
acid and add 13.5 M ammonia dropwise until all the sulphamic acid has dissolved. On addition of an
excess of 13.5M ammonia a violet colour is produced which changes to violet-blue.

B. To a neutral solution of the substance being examined add a solution of calcium chloride; no
precipitate is produced. Boil the solution; a white precipitate is produced which is soluble in 6 M acetic
acid.

Esters

To about 30 mg of the substance being examined or to the prescribed quantity add 0.5 ml of a 7%
w/v solution of hydroxylamine hydrochloride in methanol and 0.5 ml of a 10% w/v solution of
potassium hydroxide in ethanol (96%). Heat to boiling, cool, acidify with 2 M hydrochloric acid and
add 0.2 ml of a 1% w/v solution of iron(III) chloride hexahydrate. A bluish red or red colour is
produced.

Iodides

A. Dissolve a quantity of the substance being examined containing about 4 mg of iodide ion in 2 ml
of water or use 2 ml of the prescribed solution. Acidify with 2M nitric acid, add 0.4 ml of silver nitrate
solution R1, shake and allow to stand; a curdy, pale yellow precipitate is produced. Centrifuge and
wash with three 1-ml quantities of water . Carry out these operations rapidly in subdued light
disregarding the fact that the supernatant solution may not become perfectly clear . Suspend the
precipitate in 2 ml of water and add 1.5 ml of 10M ammonia; the precipitate does not dissolve.

B. To 0.2 ml of a solution of the substance being examined containing about 5 mg of iodide ion per
ml or to 0.2 ml of the prescribed solution add 0.5 ml of 1M sulphuric acid, 0.1 ml of potassium
dichromate solution, 2 ml of water and 2 ml of chloroform. Shake for a few seconds and allow to
stand. The chloroform layer is violet or violet-red.

Iron and iron salts

A. To a quantity of the substance being examined containing about 10 mg of iron( II) dissolved in 1
ml of water or to 1 ml of the prescribed solution add 1 ml of potassium hexacyanoferrate(III) solution.
A blue precipitate is produced which is insoluble in 2 M hydrochloric acid (iron(II) salts).

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Appendix VIII A. Non-aqueous titration

(No Ph. Eur. method)Method I

Dissolve the prescribed quantity of the substance being examined in a suitable volume of anhydrous
acetic acid previously neutralised using the indicator specified in the monograph, warming and
cooling if necessary, or prepare a solution as directed. When the substance is a salt of hydrochloric
or hydrobromic acid, add 15 ml of mercury(II) acetate solution before neutralising the solvent, unless
otherwise directed in the monograph. Titrate with 0.1 M perchloric acid VS to the colour change of the
indicator that corresponds to the maximum absolute value of dE/dV (where E is the electromotive
force and V is the volume of titrant) in a potentiometric titration, Appendix VIII B, of the substance
being examined. The indicator specified in the monograph is also used for the neutralisation of the
mercury(II) acetate solution and the standardisation of the titrant.

When the temperature (t2) of the titrant at the time of the assay differs from the temperature (t1) of
the titrant when it was standardised, multiply the volume of the titrant required by [1+0.0011( t1 - t2)]
and calculate the result of the assay from the corrected volume.

Carry out a blank titration when necessary.

Method II

The titrant, solvent and, where necessary, the indicator to be used are stated in the monograph.

Protect the solution and titrant from atmospheric carbon dioxide and moisture throughout the
determination.

Dissolve the substance being examined in a suitable volume of the solvent previously neutralised to
the indicator, warming and cooling if necessary, or prepare a solution as directed. Titrate to the
colour change of the indicator that corresponds to the maximum absolute value of dE/dV (where E is
the electromotive force and V is the volume of titrant) in a potentiometric titration, Appendix VIII B, of
the substance under examination. The titrant is standardised using the same solvent and indicator
as specified for the substance.

Carry out a blank titration when necessary.

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