Action and use
Rifamycin antituberculosis drug.
DEFINITION
Rifampicin Oral Suspension is a suspension of Rifampicin in powder of suitable fineness in a suitable flavoured vehicle.
The oral suspension complies with the requirements stated under Oral Liquids and with the following requirements.
Content of rifampicin, C43H58N4O12
90.0 to 110.0% of the stated amount.
IDENTIFICATION
To a quantity containing 0.1 g of Rifampicin add 30 mL of water and shake with two 50 mL quantities of chloroform. Dry the combined extracts with anhydrous sodium sulfate, filter and evaporate the filtrate to dryness at a temperature not exceeding 70°. The residue, after washing with 1 mL of ether and drying at 70°, complies with the following tests.
A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of rifampicin (RS 312).
B. Dissolve 10 mg of the residue in 10 mL of methanol and dilute 2 mL to 100 mL with phosphate buffer pH 7.4. The light absorption of the resulting solution, Appendix II B, in the range 240 to 500 nm exhibits three maxima, at 254, 334 and
475 nm.
TESTS
Acidity
pH, 4.2 to 4.8, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the solvent mixture described below. To 10 volumes of a 21.01% w/v solution of citric acid add 23 volumes of a 13.61% w/v solution of potassium dihydrogen orthophosphate, 77 volumes of a 17.42% w/v solution of dipotassium hydrogen orthophosphate, 250 volumes of acetonitrile and 640 volumes of water and mix. Prepare the solutions immediately before use.
(1) Add 5 mL of water to a quantity of the oral suspension containing 20 mg of Rifampicin and extract with four 10-mL quantities of dichloromethane, filter the combined extracts and evaporate to dryness at a temperature not exceeding 40°.
Dissolve the residue in 10 mL of acetonitrile and dilute 5 mL of the solution to 50 mL with the solvent mixture.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) 0.00030% w/v of rifampicin quinone EPCRS.
(4) 0.00020% w/v of rifampicin N-oxide BPCRS.
(5) 0.0010% w/v of 3-formylrifamycin SV BPCRS.
(6) Dilute 1 volume of solution (3) to 1.5 volumes and mix 1 volume of the resulting solution with 1 volume of solution (2).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 μm) (Partisil C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 μL of each solution.
(g) For solution (1) allow the chromatography to proceed for at least 3 times the retention time of the peak due to rifampicin.
MOBILE PHASE
35 volumes of acetonitrile and 65 volumes of a solution containing 0.1% v/v of orthophosphoric acid, 0.19% w/v of sodium perchlorate, 0.59% w/v of citric acid and 2.09% w/v of potassium dihydrogen orthophosphate.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (6), the resolution factor between the two principal peaks is at least 4.0. If necessary, adjust the concentration of acetonitrile in the mobile phase.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to rifampicin quinone is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (1.5%);
the area of any peak corresponding to rifampicin N-oxide is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (1%);
the area of any peak corresponding to 3-formylrifamycin SV is not greater than the area of the principal peak in the chromatogram obtained with solution (5) (5%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peaks eluting before the peak due to rifampicin quinone.
ASSAY
Dilute a weighed quantity containing 0.4 g of Rifampicin to 500 mL with methanol, mix thoroughly, dilute 2 mL to 100 mL with phosphate buffer pH 7.4 and measure the absorbance of the resulting solution at the maximum at 475 nm, Appendix II B. Calculate the content of C43H58N4O12 taking 187 as the value of A(1%, 1 cm) at 475 nm. Determine the weight per mL of the oral suspension, Appendix V G, and calculate the content of C43H58N4O12, weight in volume.
