Browse: British Pharmacopoeia 2009
British Pharmacopoeia Volume I & II
Monographs: Medicinal and Pharmaceutical Substances
Dicloxacillin Sodium
Dicloxacillin Sodium
General Notices
(Ph Eur monograph 0663)
C19H16Cl2N3NaO5S,H2O��510.3��13412-64-1
Action and use
Penicillin antibacterial.
Ph Eur
DEFINITION
Sodium (2S,5R,6R)-6-[[[3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]-3,3-
dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate monohydrate.
Semi-synthetic product derived from a fermentation product.
Content
95.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance
White or almost white, hygroscopic, crystalline powder.
Solubility
Freely soluble in water, soluble in ethanol (96 per cent) and in methanol.
IDENTIFICATION
First identification�A, D.
Second identification�B, C, D.
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�A. Infrared absorption spectrophotometry (2.2.24).
Preparation�Discs.
Comparison�dicloxacillin sodium CRS.
�B. Thin-layer chromatography (2.2.27).
Test solution�Dissolve 25 mg of the substance to be examined in 5 ml of water R.
Reference solution (a)�Dissolve 25 mg of dicloxacillin sodium CRS in 5 ml of water R.
Reference solution (b)�Dissolve 25 mg of cloxacillin sodium CRS, 25 mg of dicloxacillin
sodium CRS and 25 mg of flucloxacillin sodium CRS in 5 ml of water R.
Plate�TLC silanised silica gel plate R.
Mobile phase�Mix 30 volumes of acetone R and 70 volumes of a 154 g/l solution of
ammonium acetate R adjusted to pH 5.0 with glacial acetic acid R.
Application�1 µl.
Development�Over a path of 15 cm.
Drying�In air.
Detection�Expose to iodine vapour until the spots appear and examine in daylight.
System suitability�Reference solution (b):
�
�— the chromatogram shows 3 clearly separated spots.
Results�The principal spot in the chromatogram obtained with the test solution is similar in
position, colour and size to the principal spot in the chromatogram obtained with reference
solution (a).
�C. Place about 2 mg in a test-tube about 150 mm long and about 15 mm in diameter.
Moisten with 0.05 ml of water R and add 2 ml of sulphuric acid-formaldehyde reagent R. Mix
the contents of the tube by swirling; the solution is slightly greenish-yellow. Place the test-
tube in a water-bath for 1 min; a yellow colour develops.
�D. It gives reaction (a) of sodium (2.3.1).
TESTS
Solution S
Dissolve 2.50 g in carbon dioxide-free water R and dilute to 25.0 ml with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and its absorbance (2.2.25) at 430 nm is not greater than 0.04.
pH (2.2.3)
5.0 to 7.0 for solution S.
Specific optical rotation (2.2.7)
+ 128 to + 143 (anhydrous substance).
Dissolve 0.250 g in water R and dilute to 25.0 ml with the same solvent.
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Related substances
Liquid chromatography (2.2.29).
Test solution (a)�Dissolve 50.0 mg of the substance to be examined in the mobile phase and
dilute to 50.0 ml with the mobile phase.
Test solution (b)�Dilute 5.0 ml of test solution (a) to 50.0 ml with the mobile phase.
Reference solution (a)�Dissolve 50.0 mg of dicloxacillin sodium CRS in the mobile phase and
dilute to 50.0 ml with the mobile phase. Dilute 5.0 ml of this solution to 50.0 ml with the mobile
phase.
Reference solution (b)�Dilute 5.0 ml of test solution (b) to 50.0 ml with the mobile phase.
Reference solution (c)�Dissolve 5 mg of flucloxacillin sodium CRS and 5 mg of dicloxacillin
sodium CRS in the mobile phase, then dilute to 50.0 ml with the mobile phase.
Column:�
�— size: l = 0.25 m, Ø = 4 mm;
�— stationary phase: octadecylsilyl silica gel for chromatography R (5 µm).
Mobile phase�Mix 25 volumes of acetonitrile R and 75 volumes of a 2.7 g/l solution of
potassium dihydrogen phosphate R adjusted to pH 5.0 with dilute sodium hydroxide solution
R.
Flow rate�1.0 ml/min.
Detection�Spectrophotometer at 225 nm.
Injection�20 µl of test solution (a) and reference solutions (b) and (c).
Run time�5 times the retention time of dicloxacillin.
Retention time�Dicloxacillin = about 10 min.
System suitability�Reference solution (c):
�— resolution: minimum 2.5 between the peaks due to flucloxacillin (1st peak) and
dicloxacillin (2 nd peak).
Limits:
�— any impurity: for each impurity, not more than the area of the principal peak in the
chromatogram obtained with reference solution (b) (1 per cent);
�— total: not more than 5 times the area of the principal peak in the chromatogram obtained
with reference solution (b) (5 per cent);
�— disregard limit: 0.05 times the area of the principal peak in the chromatogram obtained
with reference solution (b) (0.05 per cent).
N,N-Dimethylaniline (2.4.26, Method B)
Maximum 20 ppm.
2-Ethylhexanoic acid (2.4.28)
Maximum 0.8 per cent m/m.
Water (2.5.12)
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3.0 per cent to 4.5 per cent, determined on 0.300 g.
Pyrogens (2.6.8)
If intended for use in the manufacture of parenteral dosage forms without a further
appropriate procedure for the removal of pyrogens, it complies with the test for pyrogens.
Inject per kilogram of the rabbit's mass 1 ml of a solution in water for injections R containing
20 mg of the substance to be examined per millilitre.
ASSAY
Liquid chromatography (2.2.29) as described in the test for related substances with the
following modifications.
Injection�Test solution (b) and reference solution (a).
System suitability�Reference solution (a):
�
�— repeatability: maximum relative standard deviation of 1.0 per cent after 6 injections.
STORAGE
In an airtight container , at a temperature not exceeding 25 °C. If the substance is sterile,
store in a sterile, airtight, tamper-proof container .
IMPURITIES
�A. R = CO2H: (4S)-2-[carboxy[[[3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]
methyl]-5,5-dimethylthiazolidine-4-carboxylic acid (penicilloic acids of dicloxacillin),
�B. R = H: (2RS,4S)-2-[[[[3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]carbonyl]amino]methyl]
-5,5-dimethylthiazolidine-4-carboxylic acid (penilloic acids of dicloxacillin),
�C. (2S,5R,6R)-6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic
acid (6-aminopenicillanic acid),
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�D. 3-(2,6-dichlorophenyl)-5-methylisoxazole-4-carboxylic acid.
Ph Eur
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