Levalbuterol Inhalation Solution
» Levalbuterol Inhalation Solution is a sterile, aqueous solution of Levalbuterol Hydrochloride, prepared with Sodium Chloride. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of levalbuterol hydrochloride (C13H21NO3·HCl).
Packaging and storage— Preserve in low-density polyethylene single-use ampuls, with a multilayer foil overwrap. Store at controlled room temperature.
Labeling— The outer label indicates the dose and that the ampuls should be discarded if the solution is not colorless.
USP Reference standards 11
USP Albuterol RS Click to View Structure
USP Levalbuterol Hydrochloride RS Click to View Structure
(R)-1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-,¢-diol hydrochloride.
USP Levalbuterol Related Compound A RS Click to View Structure
4-(2-tert-Butylamino-ethyl)-2-hydroxymethyl-phenol.
USP Levalbuterol Related Compound B RS Click to View Structure
[{(1,1-Dimethylethyl)amino}methyl]-4-hydroxy-3-methyl-benzenemethanol.
USP Levalbuterol Related Compound C RS Click to View Structure
[{(1,1-Dimethylethyl)amino}methyl]-4-hydroxy-3-(methoxymethyl)-benzenemethanol.
USP Levalbuterol Related Compound D RS Click to View Structure
5-[2-{(1,1-Dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxy-benzaldehyde.
USP Levalbuterol Related Compound E RS Click to View Structure
[{(1,1-Dimethylethyl)amino}methyl]-3-(ethoxymethyl)-4-hydroxy-benzenemethanol.
USP Levalbuterol Related Compound F RS Click to View Structure
[{(1,1-Dimethylethyl)amino}methyl]-4-(phenylmethoxy)-1,3-benzenedimethanol.
USP Levalbuterol Related Compound G RS Click to View Structure
[{(1,1-Dimethylethyl)amino}methyl]-4,5-dihydroxy-1,3-benzenedimethanol.
Identification—
A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that observed in the chromatogram of the Standard preparation, as obtained in the Assay.
Color 631: not more than 20 APHA platinum cobalt units.
Sterility 71: meets the requirements.
Uniformity of dosage units 905: meets the requirements.
pH 791: between 3.3 and 4.5.
Particulate matter 788: not more than 250 particles greater than or equal to 10 µm; not more than 25 particles greater than or equal to 25 µm; not more than 2 particles greater than or equal to 100 µm; and not more than 1 particle greater than or equal to 300 µm.
Osmolality 785: between 280 and 320 mOsmol per kg.
Related compounds—
Mobile phase and Chromatographic system— Proceed as directed for Related compounds under Levalbuterol Hydrochloride.
Diluent— Dissolve about 9.0 ± 0.05 g of sodium chloride in 950 mL of water. Adjust with dilute sulfuric acid to a pH of 4.0, and dilute with water to 1000 mL. Mix, and pass through 0.45-µm filter.
Standard solution— Dissolve accurately weighed quantities of USP Levalbuterol Hydrochloride RS, USP Levalbuterol Related Compound A RS, USP Levalbuterol Related Compound B RS, USP Levalbuterol Related Compound C RS, USP Levalbuterol Related Compound D RS, USP Levalbuterol Related Compound E RS, USP Levalbuterol Related Compound F RS, and USP Levalbuterol Related Compound G RS in Diluent to obtain a solution having known concentrations of about 0.05 µg per mL of each related compound and 100 µg per mL of USP Levalbuterol Hydrochloride RS.
Test solution— Use the Assay preparation, prepared as directed in the Assay.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Determine the area of the levalbuterol peak, and integrate all the peaks with an area greater than 0.05% of the area corresponding to levalbuterol hydrochloride. Calculate the percentage of each impurity in the portion of Inhalation Solution taken by the formula:
100(ri / rs)(1/F)
in which F is the relative response factor for each impurity and is equal to 1.0 for related compounds A, B, C, E, and G and all unknown peaks, 3.0 for related compound D, and 1.2 for related compound F; ri is the peak response for each impurity obtained from the Test solution; and rs is the sum of the responses of all the peaks: not more than 0.10% of related compound G is found; not more than 0.08% of related compound D in each ampul is found (total content of related compound D should not be more than 1.0 µg per ampul); not more than 0.25% of total unknown impurities is found; not more than 0.10% of any unknown impurity is found; and not more than 0.70% of total impurities is found.
Enantiomeric purity and chiral identity—
Mobile phase, Sensitivity solution, and Standard solution— Proceed as directed for Enantiomeric purity and chiral identity under Levalbuterol Hydrochloride.
Test solution— All sample concentrations are injected neat.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 225-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L63. The flow rate is about 1.0 mL per minute. The minimum run time is 30 minutes. Inject 10 µL of the Sensitivity solution. The resolution, R, between levalbuterol and (S)-albuterol is not less than 3.0; and the tailing factors for levalbuterol and (S)-albuterol are not more than 1.6 and 2.0, respectively. Inject the Sensitivity solution three times, and relative standard deviation calculated from the peak area of (S)-albuterol is not greater than 20%.
Procedure— Inject equal volumes of the Standard solution and the Test solution such that approximately 4.2 µg of levalbuterol are injected. The percentage of (S)-albuterol is calculated using the following equation:
100(ri / rs)
in which ri is the peak response for (S)-albuterol, and rs is the sum of the responses of both levalbuterol and (S)-albuterol peaks. The Test solution contains not more than 2.50% (S)-albuterol.
Assay—
Solution A, Solution B, Mobile phase, and Chromatographic system— Proceed as directed in the Assay under Levalbuterol Hydrochloride.
Diluent— Dissolve about 9.0 ± 0.05 g of sodium chloride in 950 mL of water. Adjust with dilute sulfuric acid to a pH of 4.0, and dilute with water to 1000 mL. Mix, and pass through 0.45-µm filter.
Standard preparation— Dissolve an accurately weighed portion of USP Levalbuterol Hydrochloride RS in Diluent to obtain a solution having a known concentration of 100 µg per mL.
Assay preparation— Transfer an accurately measured volume of Inhalation Solution to a suitable volumetric flask, and quantitatively dilute with Diluent to obtain a solution having a concentration of about 100 µg of levalbuterol hydrochloride per mL.
Procedure— Separately inject equal volumes (about 10 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 concentration, in µg per mL, of C13H21NO3·HCl per ampul by the formula:
DC(rU / rS)
in which D is the dilution factor; C is the concentration of USP Levalbuterol Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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