Action and use
Beta2-adrenoceptor agonist; bronchodilator.
DEFINITION
Salbutamol Tablets contain Salbutamol Sulfate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of salbutamol, C13H21NO3
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. In the Assay, record the UV spectrum of the principal peak in the chromatograms obtained with solutions (1) and (2) with a diode array detector in the range of 210 to 400 nm.
The UV spectrum of the principal peak in the chromatogram obtained with solution (1) is concordant with that of the peak in the chromatogram obtained with solution (2); the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).
B. Shake a quantity of the powdered tablets containing the equivalent of 4 mg of salbutamol with 10 mL of water and filter. The filtrate yields the reactions characteristic of sulfates, Appendix VI.
TESTS
Dissolution
Carry out the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 500 mL of 0.01M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes withdraw a sample of the medium and filter (a 0.45-μm cellulose acetate filter is suitable). Dilute with the dissolution medium, if necessary, to produce a solution expected to contain the equivalent of 0.0004% w/v of salbutamol.
(2) 0.00048% w/v of salbutamol sulfate BPCRS in water.
(3) 0.04% w/v of 2-tert-butylamino-1-(4-hydroxy-3-methylphenyl)ethanol BPCRS (impurity C) and 0.048% w/v of salbutamol sulfate BPCRS in methanol (10%).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with cyanosilyl silica gel for chromatography (5 μm) (Spherisorb CN is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 276 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
5 volumes of propan-2-ol, 30 volumes of 0.05M ammonium acetate and 65 volumes of water, adjusted to pH 4.5 with glacial acetic acid.
When the chromatograms are recorded under the prescribed conditions, the retention time of salbutamol is about 2 minutes.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to salbutamol and impurity C is at least 1.5.
DETERMINATION OF CONTENT
Calculate the total content of salbutamol, C13H21NO3, in the medium from the chromatograms obtained and using the declared content of C13H21NO3 in salbutamol sulfate BPCRS.
LIMITS
The amount of salbutamol released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Disperse a quantity of the powdered tablets in sufficient mobile phase to produce a solution containing the equivalent of 0.02% w/v of salbutamol and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes and further dilute 1 volumes of this solution to 5 volumes.
(3) 0.02% w/v of salbutamol for peak identification EPCRS.
(4) 0.02% w/v of salbutamol impurity standard BPCRS.
(5) 0.00004% w/v of each of salbutamol sulfate BPCRS and salbutamol impurity B BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octylsilyl silica gel for chromatography (5 μm) (Symmetry C8 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 220 nm.
(f) Inject 20 μL of each solution.
(g) For solution (1), allow the chromatography to proceed for 25 times the retention time of salbutamol.
MOBILE PHASE
22 volumes of acetonitrile R1 and 78 volumes of a solution containing 0.287% w/v of sodium heptanesulfonate and 0.25% w/v of potassium dihydrogen orthophosphate adjusted to pH 3.7 with 2M orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between the peaks due to salbutamol and impurity B is at least 3.0.
CALCULATION OF IMPURITIES
For each impurity, use the concentration of salbutamol in solution (2).
For the reporting threshold, use the concentration of salbutamol in solution (2).
For peak identification, use solutions (3) and (4).
Salbutamol retention time: about 3 minutes.
Relative retention: impurity B, about 1.4; impurity D, about 2.7; impurity F, about 6.3.
Correction factors: impurity D, multiply by 0.5.
LIMITS
— impurity F: not more than 0.8%;
— impurity D: not more than 0.6%;
— unspecified impurities: for each impurity, not more than 0.2%;
— total impurities: not more than 2.0%;
— reporting threshold: 0.1%.
Uniformity of content
Tablets containing less than the equivalent of 2 mg and/or less than 2% w/w of salbutamol comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add 50 mL of 0.05M hydrochloric acid to one tablet, shake for 1 hour, add sufficient 0.05M hydrochloric acid to produce 100 mL, mix, centrifuge and use the supernatant liquid.
(2) 0.0024% w/v of salbutamol sulfate BPCRS in water.
(3) 0.05% w/v of 2-tert-butylamino-1-(4-hydroxy-3-methylphenyl)ethanol BPCRS (impurity C) and 0.06% w/v of salbutamol sulfate BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to salbutamol and impurity C is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of C13H21NO3 in each tablet using the declared content of C13H21NO3 in salbutamol sulfate BPCRS.
ASSAY
For tablets containing the equivalent of less than 2 mg and/or less than 2% w/w of salbutamol
Use the average of the individual results determined in the test for Uniformity of content.
For tablets containing the equivalent of 2 mg or more and 2% w/w or more of salbutamol
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake 10 tablets with 100 mL of water for 1 hour, add sufficient water to produce a solution containing the equivalent of 0.04% w/v of salbutamol, mix, centrifuge and use the supernatant liquid.
(2) 0.048% w/v of salbutamol sulfate BPCRS in water.
(3) 0.04% w/v of 2-tert-butylamino-1-(4-hydroxy-3-methylphenyl)ethanol BPCRS (impurity C) and 0.048% w/v of salbutamol sulfate BPCRS in methanol (10%).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to salbutamol and impurity C is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of salbutamol, C13H21NO3, in the tablets from the chromatograms obtained and using the declared content of C13H21NO3 in salbutamol sulfate BPCRS.
LABELLING
The quantity of active ingredient is stated in terms of the equivalent amount of salbutamol.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B, C, D, E, F, G, H, I, J and P listed under Salbutamol Sulfate.
