Levalbuterol Hydrochloride
(R)-1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-,¢-diol hydrochloride [50293-90-8]. » Levalbuterol Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C13H21NO3·HCl, calculated on the anhydrous basis.
Packaging and storage
Preserve in tight, light-resistant containers, and store at controlled room temperature.
USP Reference standards 11
USP Albuterol RS . USP Dehydrated Alcohol RS . USP Ethyl Acetate RS . USP Heptane RS . 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 . USP Methyl Alcohol RS . USP 2-Propanol RS .
Identification,
Infrared Absorption 197K.
pH 791:
between 4.5 and 5.5, in a solution (1 in 100).
Water, Method Ic 921:
not more than 0.3%.
Residue on ignition 281:
not more than 0.1%.
Heavy metals, Method I 231:
not more than 10 ppm.
Microbial enumeration tests 61 and Tests for specified microorganisms 62:
meets the requirements of the tests for absence of Salmonella species, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The total aerobic bacterial count is less than 10 cfu per g. The total combined molds and yeasts count is less than 10 cfu per g.
Add the following:
Related compounds
Solution A, Solution B, Mobile phase, and Diluent
Proceed as directed in the Assay.
Test solution
Use the Assay preparation.
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, and USP Levalbuterol Related Compound F 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.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The column temperature is maintained at 45. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows.
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 peaks with an area greater than 0.05% of the area corresponding to the levalbuterol peak. Calculate the percentage of each impurity in the portion of Levalbuterol Hydrochloride taken by the formula:
100(ri / rs F)
in which ri is the peak response for each impurity obtained from the Test solution; rs is the sum of the responses of all the peaks (see Table 1 for limits of individual impurities); and F is the relative response factor for each impurity. Not more than 0.5% of total impurities is found.
Table 1
Enantiomeric purity and chiral identity
Mobile phase
Prepare a degassed mixture of acetonitrile, methanol, acetic acid, and triethylamine (500: 500: 3: 1).
Diluent
Use the Mobile phase.
Sensitivity solution
Dissolve about 10 mg of USP Levalbuterol Hydrochloride RS and 40 µg of USP Albuterol RS in 100 mL of Diluent, and mix.
Standard solution
Dissolve an accurately weighed quantity of USP Albuterol RS in Diluent to obtain a solution having a known concentration of about 1.5 mg per mL.
Test solution
Transfer an accurately weighed quantity of Levalbuterol Hydrochloride to a suitable volumetric flask, and quantitatively dilute with Diluent to obtain a solution having a concentration of about 0.8 mg per mL of levalbuterol hydrochloride.
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 mL per minute. Chromatograph the Sensitivity solution, and record the peak responses as directed for Procedure: the resolution, R, between levalbuterol and (S)-albuterol is not less than 2.0; the column efficiency calculated from either peak is not less than 4000; the tailing factor for levalbuterol and (S)-albuterol is not more than 2.2. The Sensitivity solution is injected three times, and the relative standard deviation for replicate injections is not more than 20% for (S)-albuterol.
Procedure
Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution. 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: not more than 0.2% of (S)-albuterol is found.
Assay
Solution A
Prepare a 1 in 1000 solution of phosphoric acid in water, and degas.
Solution B
Prepare a degassed mixture of acetonitrile, methanol, water, and phosphoric acid (700: 700: 600: 2).
Mobile phase
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent
Use Solution A.
Standard preparation
Dissolve an accurately weighed quantity of USP Levalbuterol Hydrochloride RS in Diluent to obtain a solution having a known concentration of about 100 µg per mL.
Assay preparation
Transfer about 10 mg of Levalbuterol Hydrochloride, accurately weighed, to a 100-mL volumetric flask. Dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The column temperature is maintained at 35. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows:
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 quantity in mg of C13H21NO3·HCl in the portion of Levalbuterol Hydrochloride taken by the formula:
0.1CS (rU / rS)
in which CS is the concentration, in µg per mL, of USP Levalbuterol Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses of levalbuterol hydrochloride obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 2762
Pharmacopeial Forum: Volume No. 33(3) Page 416
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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