BP 2025 (Ph. Eur. 11.6 update)
Action and use
Penicillin antibacterial.
DEFINITION
Flucloxacillin Infusion is a sterile solution containing Flucloxacillin Sodium Monohydrate and a suitable buffer. It is supplied as a ready-to-use solution.
The infusion complies with the requirements stated under Parenteral Preparations and with the following requirements. Where appropriate, the infusion also complies with the requirements stated under Unlicensed Medicines.
Content of flucloxacillin, C19H17ClFN3O5S
90.0 to 105.0% of the stated amount.
CHARACTERS
A clear, colourless solution.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Dilute a volume of the infusion with sufficient phosphate buffer pH 7.0 to produce a solution containing the equivalent of 0.25% w/v of flucloxacillin.
(2) 0.25% w/v of flucloxacillin sodium BPCRS in phosphate buffer pH 7.0.
(3) 0.25% w/v of each of cloxacillin sodium BPCRS, dicloxacillin sodium BPCRS and flucloxacillin sodium BPCRS in phosphate buffer pH 7.0.
CHROMATOGRAPHIC CONDITIONS
(a) Use a TLC silica gel silanised plate (Merck silanised silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 1 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air, expose to iodine vapour until the spots appear and examine in
daylight.
MOBILE PHASE
30 volumes of acetone and 70 volumes of a 15.4% w/v solution of ammonium acetate adjusted to pH 5.0 with glacial acetic acid.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows three clearly separated spots.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) is similar in position, colour and size to that in the
chromatogram obtained with solution (2).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of
the principal peak in the chromatogram obtained with solution (2).TESTS
Acidity or alkalinity
pH, 5.5 to 7.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a volume of the infusion with sufficient of the mobile phase to produce a solution containing the equivalent of
0.1% w/v of flucloxacillin.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) Dilute 1 volume of solution (2) to 10 volumes with the mobile phase.
(4) 0.01% w/v of each of cloxacillin sodium BPCRS and flucloxacillin sodium BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Hypersil 5 ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 225 nm.
(f) Inject 20 μL of each solution.
(g) For solution (1), allow the chromatography to proceed for six times the retention time of the principal peak.
MOBILE PHASE
25 volumes of acetonitrile and 75 volumes of a 0.27% w/v solution of potassium dihydrogen orthophosphate adjusted to pH 5.0 with 2M sodium hydroxide.
When the chromatograms are recorded under the prescribed conditions, the retention time of flucloxacillin is about 12 minutes and the relative retention of cloxacillin is about 0.8.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to cloxacillin and flucloxacillin is at least 2.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);
the sum of the areas of any secondary peaks is not greater than five times the area of the principal peak in the chromatogram obtained with solution (2) (5%).
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (3) (0.05%).
Bacterial endotoxins
Dilute the infusion with water BET to contain the equivalent of 9 mg of flucloxacillin per mL (solution A). The endotoxin limit concentration of solution A is 3.5 IU per mL, Appendix XIV C.
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a volume of the infusion with sufficient of the mobile phase to produce a solution containing the equivalent of 0.1% w/v of flucloxacillin; dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.
(2) 0.011% w/v of flucloxacillin sodium BPCRS in the mobile phase.
(3) 0.01% w/v of each of cloxacillin sodium BPCRS and flucloxacillin sodium BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The Assay is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to cloxacillin and flucloxacillin is at least 2.5.
DETERMINATION OF CONTENT
Calculate the content of C19H17ClFN3O5S in the infusion using the declared content of C19H16ClFN3NaO5S in flucloxacillin sodium BPCRS. Each mg of C19H16ClFN3NaO5S is equivalent to 0.9538 mg of C19H17ClFN3O5S.
STORAGE
Flucloxacillin Infusion should be stored at a temperature of 2° to 8°.
LABELLING
The quantity of active ingredient is stated in terms of the equivalent amount of flucloxacillin.
