» Albuterol Tablets contain an amount of albuterol sulfate [(C13H21NO3)2·H2SO4] equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of albuterol (C13H21NO3).
Packaging and storage Preserve in tight, light-resistant containers, and store at controlled room temperature.
USP Reference standards 11
A: The RF value of the principal spot obtained from the Test preparation corresponds to that obtained from Standard solution A in the chromatograms obtained as directed in the test for Related compounds.
B: Shake a quantity of the powdered Tablets, equivalent to about 4 mg of Albuterol, with 10 mL of water and filter: the filtrate responds to the tests for Sulfate 191.
Dissolution, Procedure for a Pooled Sample 711
Medium: water; 500 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Determine the amount of C13H21NO3 dissolved using the following method.
Mobile phase, Standard preparation, and Chromatographic system Prepare as directed in the Assay.
Procedure Inject a suitable volume (about 100 µL) of a portion of the solution under test, previously passed through a 0.45-µm nylon filter, into the chromatograph, record the chromatogram, and measure the response for the major peak. Calculate the quantity of C13H21NO3 dissolved by comparing this peak response with the major peak response similarly obtained on chromatographing the Standard preparation previously diluted, if necessary, with a mixture of water and methanol (6:4) to obtain a Standard solution having a known concentration of USP Albuterol Sulfate RS approximately corresponding to the concentration of the solution under test.
Tolerances Not less than 80% (Q) of the labeled amount of C13H21NO3 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Test preparation Place a quantity of finely powdered Tablets, equivalent to 48 mg of albuterol, into a suitable container. Add 60 mL of diluted alcohol (1 in 2), and shake by mechanical means for 30 minutes. Filter the mixture, and wash the filter with small portions of alcohol, combining this with the filtrate. Evaporate the filtrate to dryness under reduced pressure at a temperature below 40. Dissolve the residue as completely as possible in 2 mL of water.
Standard solutions Prepare solutions of USP Albuterol Sulfate RS in water having known concentrations of 0.580 mg per mL (Solution A), 0.218 mg per mL (Solution B), and 0.073 mg per mL (Solution C) equivalent to 0.483 mg, 0.183 mg, and 0.061 mg, respectively, of albuterol.
Procedure Apply 10 µL aliquots (in two successive portions of 5 µL, allowing the solvent to evaporate between applications) of the Test preparation and each of Standard solutions A, B, and C to separate points to a suitable chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Air-dry, and place the plate in a saturated chromatographic chamber. Develop the chromatograms with a solvent system consisting of a mixture of methyl isobutyl ketone, isopropyl alcohol, ethyl acetate, water, and ammonium hydroxide (50:45:35:18:3) until the solvent front has moved about 17 cm. Remove the plate from the developing chamber, air-dry, and spray first with 3-methyl-2-benzothiazolinone hydrazone hydrochloride TS, then with ammoniacal potassium ferricyanide TS, and finally again with 3-methyl-2-benzothiazolinone hydrazone hydrochloride TS. Examine the plate and estimate the responses of any secondary spots observed in the lane of the Test preparation by comparison with those of Standard solutions A, B, and C. No major secondary spot is greater in size or intensity than the principal spot produced by Standard solution A (2.0%). No other secondary spot is greater in size or intensity than the principal spot produced by Standard solution B (0.75%). No more than two other secondary spots are equal in size or intensity than the principal spot produced by Standard solution C (0.25%). The sum of the intensities of all secondary spots obtained from the Test preparation corresponds to not more than 3.5%.
1% Acetic acid Transfer a 20-mL portion of glacial acetic acid to a suitable volumetric flask, and dilute with water to 2000 mL.
Mobile phase Dissolve 1.13 g of sodium 1-hexanesulfonate in 1200 mL of water, add 12 mL of glacial acetic acid, and mix. Prepare a filtered and degassed mixture of this solution and methanol (6:4). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Transfer about 12 mg of USP Albuterol Sulfate RS, accurately weighed, to a 100-mL volumetric flask. Add 60 mL of 1% Acetic acid, sonicate for 5 minutes, dilute with methanol to volume, and mix. Pipet 25 mL of this solution into a 100-mL volumetric flask, dilute with a mixture of water and methanol (6:4) to volume, and mix.
Assay preparation Transfer a number of whole Tablets, equivalent to about 50 mg of albuterol, to a 2000-mL volumetric flask. Add 1200 mL of 1% Acetic acid, shake by mechanical means for 45 minutes, sonicate for 10 minutes, allow to cool to room temperature, dilute with methanol to volume, and mix. Pass through a suitable filter having a 0.45-µm or finer porosity.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 276-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency determined from the analyte peak is not less than 800 theoretical plates; the tailing factor for the analyte peak is not more than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 25 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of albuterol (C13H21NO3) in the number of Tablets taken by the formula:
2000C(rU / rS)(2)(239.31/576.70)in which 2000 is the volume, in mL, of the Assay preparation; C is the concentration, in mg per mL, of USP Albuterol Sulfate RS in the Standard preparation; rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively; 2 is the number of molecules of albuterol released from each molecule of albuterol sulfate; and 239.31 and 576.70 are the molecular weights of albuterol and albuterol sulfate, respectively.
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