Levalbuterol Hydrochloride
(lev'' al bue' ter ol hye'' droe klor' ide).
C13H21NO3·HCl 275.77 (R)-1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-,¢-diol hydrochloride [50293-90-8]. DEFINITION
Levalbuterol Hydrochloride contains NLT 98.0% and NMT 102.0% of C13H21NO3·HCl, calculated on the anhydrous basis.
IDENTIFICATION
ASSAY
• Procedure
Solution A:
1 in 1000 solution of phosphoric acid in water
Solution B:
Acetonitrile, methanol, phosphoric acid, and water (350:350:1:300)
Mobile phase:
See the gradient table below.
Diluent:
Solution A
Standard solution:
100 µg/mL of USP Levalbuterol Hydrochloride RS in Diluent
Sample solution:
100 µg/mL of Levalbuterol Hydrochloride in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
35
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
Greater than 5500 theoretical plates
Tailing factor:
Less than 2.3
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C13H21NO3·HCl in the portion of Levalbuterol Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
98.0%102.0% on the anhydrous basis
IMPURITIES
Organic Impurities
• Procedure 1
Solution A, Solution B, Diluent, and Sample solution:
Proceed as directed in the Assay.
Standard solution:
[NotePrepare a solution containing the following in Diluent. ]
USP Levalbuterol Hydrochloride RS, 100 µg/mL
USP Levalbuterol Related Compound A RS, 0.05 µg/mL
USP Levalbuterol Related Compound B RS, 0.05 µg/mL
USP Levalbuterol Related Compound C RS, 0.05 µg/mL
USP Levalbuterol Related Compound D RS, 0.05 µg/mL
USP Levalbuterol Related Compound E RS, 0.05 µg/mL
USP Levalbuterol Related Compound F RS, 0.05 µg/mL
USP Levalbuterol Related Compound H RS, 0.05 µg/mL
Mobile phase:
See the gradient table below.
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
45
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 4.9 between levalbuterol and levalbuterol related compound A; NLT 1.5 between levalbuterol related compound B and levalbuterol related compound C
Column efficiency:
NLT 4000 for levalbuterol
Tailing factor:
NMT 4.0 for levalbuterol
Relative standard deviation:
Less than 20% from any of the six related compound peaks
Analysis
Samples:
Standard solution and Sample solution
[NoteIntegrate 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:
Result = (rU/rT) × (1/F) × 100
Acceptance criteria:
See Impurity Table 1.
Impurity Table 1
• Procedure 2: Enantiomeric Purity and Chiral Identity
Mobile phase:
Acetonitrile, methanol, acetic acid, and triethylamine (500:500:3:1)
Diluent:
Mobile phase
System suitability solution A:
0.10 mg/mL of USP Levalbuterol Hydrochloride RS and 0.40 µg/mL of USP Albuterol RS in Diluent
System suitability solution B:
1.5 mg/mL of USP Albuterol RS in Diluent
Sample solution:
0.8 mg/mL of Levalbuterol Hydrochloride in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 225 nm
Column:
4.6-mm × 25-cm; 5-µm packing L63
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Sample:
System suitability solution A
Suitability requirements
Resolution:
NLT 2.0 between levalbuterol and (S)-albuterol
Column efficiency:
NLT 4000, calculated from either peak
Tailing factor:
NMT 2.2 for levalbuterol and (S)-albuterol
Relative standard deviation:
NMT 20% for (S)-albuterol, injected three times
Analysis
Samples:
System suitability solution B and Sample solution
Calculate the percentage of (S)-albuterol in the portion of Levalbuterol Hydrochloride taken:
Result = (rU/rT) × 100
Acceptance criteria:
NMT 0.2% of (S)-albuterol
SPECIFIC TESTS
• Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62:
The total aerobic bacterial count is less than 10 cfu/g. The total combined molds and yeasts count is less than 10 cfu/g. It meets the requirements of the tests for absence of Salmonella species, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.
• pH 791:
4.55.5, in a 10-mg/mL solution
• Water Determination, Method Ic 921:
NMT 0.3%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store at controlled room temperature.
• USP Reference Standards 11
USP Levalbuterol Hydrochloride RS
(R)-1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-,¢-diol hydrochloride.
USP Levalbuterol Related Compound B RS
[{(1,1-Dimethylethyl)amino}methyl]-4-hydroxy-3-methyl-benzenemethanol.
USP Levalbuterol Related Compound C RS
[{(1,1-Dimethylethyl)amino}methyl]-4-hydroxy-3-(methoxymethyl)-benzenemethanol.
USP Levalbuterol Related Compound D RS
5-[2-{(1,1-Dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxy-benzaldehyde.
USP Levalbuterol Related Compound E RS
[{(1,1-Dimethylethyl)amino}methyl]-3-(ethoxymethyl)-4-hydroxy-benzenemethanol.
USP Levalbuterol Related Compound F RS
[{(1,1-Dimethylethyl)amino}methyl]-4-(phenylmethoxy)-1,3-benzenedimethanol.
USP Levalbuterol Related Compound H RS
4-[2-(tert-Butylamino)-1-methoxyethyl]-2-(hydroxymethyl)phenol. C14H23NO3 253.34
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3654
Pharmacopeial Forum: Volume No. 36(3) Page 670
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