Albuterol Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Albuterol Tablets contain an amount of albuterol sulfate [(C₁₃H₂₁NO₃)₂ · H₂SO₄] equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of albuterol (C₁₃H₂₁NO₃).

2 IDENTIFICATION

Change to read:

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.(USP 1-May-2023)

Change to read:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-May-2023)

3 ASSAY

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Procedure  

Solution A: 10 mL/L of glacial acetic acid in water

Solution B: 1.13 g of sodium 1-hexanesulfonate in 1200 mL of water. Add 12 mL of glacial acetic acid.

Diluent: Methanol and water (40:60)

Mobile phase: Methanol and Solution B (40:60)

Standard stock solution: 0.12 mg/mL of USP Albuterol Sulfate RS prepared as follows. Transfer a suitable amount of USP Albuterol Sulfate RS to a suitable volumetric ask. Add 60% of the ask volume of Solution A and sonicate for about 5 min. Dilute with methanol to volume.(USP 1-May-2023)

Standard solution: 0.03 mg/mL of USP Albuterol Sulfate RS (USP 1-May-2023) from Standard stock solutionin Diluent (USP 1-May-2023) Sample solution: Nominally 0.025 mg/mL of albuterol prepared as follows. Transfer a number of whole Tablets, equivalent to 50 mg of albuterol, to a suitable volumetric ask. Add 60% of the ask volume of Solution A, shake by mechanical means for about (USP 1-May-2023) 45 min, and sonicate for about (USP 1-May-2023) 10 min. Allow to cool to room temperature and dilute with methanol to volume. Pass through a suitable lter of 0.45-µm or ner pore size.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 276 nm. For Identication B, use a diode array detector in the range of 200–400 nm. (USP 1-May-2023) Column: 4.6-mm × 15-cm; 5-µm (USP 1-May-2023) packing L1

Flow rate: 1.5 mL/min

Injection volume: 25 µL

Run time: NLT 2.5 times the retention time of albuterol (USP 1-May-2023)

System suitability

Sample: Standard solution

Suitability requirements

 (USP 1-May-2023)

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

3.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of albuterol (C₁₃H₂₁NO₃) in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × M × (M_r1 /M_r2) × 100

r_U = peak response of albuterol (USP 1-May-2023) from the Sample solution  

r_S = peak response of albuterol (USP 1-May-2023) from the Standard solution

C_S = concentration of USP Albuterol Sulfate RS in the Standard solution (mg/mL)

C_U = nominal concentration of albuterol in the Sample solution (mg/mL)

M = number of moles of albuterol per mole of albuterol sulfate, 2

M_r1 = molecular weight of albuterol, 239.31  

M_r2 = molecular weight of albuterol sulfate, 576.70  

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

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Dissolution 〈711〉 (USP 1-May-2023)

Medium: Water; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Diluent, Mobile phase, and Standard stock solution: Prepare as directed in the Assay.

Standard solution: 0.03 mg/mL of USP Albuterol Sulfate RS in Diluent, from Standard stock solution. If necessary, dilute with Diluent to a concentration corresponding to the Sample solution.

Sample solution: Pass a portion of the solution under test through a suitable (USP 1-May-2023) lter of 0.45-µm pore size. Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 276 nm

Column: 4.6-mm × 15-cm; 5-µm (USP 1-May-2023) packing L1

Flow rate: 1.5 mL/min

Injection volume: 100 µL

Run time: NLT 2.5 times the retention time of albuterol (USP 1-May-2023)

System suitability

Sample: Standard solution

Suitability requirements

(USP 1-May-2023)

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of albuterol (C₁₃H₂₁NO₃) dissolved:

Result = (r_U /r_S) × C_S × V × M × (M_r1 /M_r2) × (1/L) × 100

r_U = peak response of albuterol from the Sample solution  

r_S = peak response of albuterol from the Standard solution

C_S = concentration of USP Albuterol Sulfate RS in the Standard solution (mg/mL)  

V = volume of Medium, 500 mL

M = number of moles of albuterol per mole of albuterol sulfate, 2

M_r1 = molecular weight of albuterol, 239.31  

M_r2 = molecular weight of albuterol sulfate, 576.70

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of albuterol (C₁₃H₂₁NO₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

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Organic Impurities

Solution A: 9.5 g/L of sodium borate in water. Adjust with a sodium hydroxide solution to a pH of 10.1.

Solution B: Acetonitrile

Mobile phase: See Table 1.

System suitability solution: 0.002 mg/mL each of USP Albuterol Related Compound B RS and USP Levalbuterol Related Compound H RS in water

Sensitivity solution: 0.001 mg/mL of USP Albuterol Sulfate RS in water

Standard solution: 0.0025 mg/mL each of USP Albuterol Sulfate RS, USP Albuterol Related Compound E RS, USP Levalbuterol Related Compound C RS, and USP Levalbuterol Related Compound D RS in water

Sample solution: Nominally 1.0 mg/mL of albuterol from Tablets prepared as follows. Transfer a number of Tablets (NLT 20) to a suitable volumetric ask and add 80% of the ask volume of water. Sonicate for 15 min. Dilute with water to volume. Pass through a suitable lter of 0.2-µm pore size.

5.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 231 nm

Column: 2.1-mm × 10-cm; 1.7-µm packing L1

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 0.37 mL/min

Injection volume: 6 µL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note—See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between levalbuterol related compound H and albuterol related compound B, System suitability solution Relative standard deviation: NMT 5.0% for albuterol, albuterol related compound E, levalbuterol related compound C, and levalbuterol related compound D, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

5.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of albuterol related compound E, levalbuterol related compound C, and levalbuterol related compound D in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of albuterol related compound E, levalbuterol related compound C, or levalbuterol related compound D from the Sample solution

r_S = peak response of albuterol related compound E, levalbuterol related compound C, or levalbuterol related compound D from the Standard solution

C_S = concentration of the corresponding Reference Standard in the Standard solution (mg/mL)  

C_U = nominal concentration of albuterol in the Sample solution (mg/mL)  

Calculate the percentage of any unspecied degradation product in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × M × (M_r1 /M_r2) × 100

r_U = peak response of each unspecied degradation product from the Sample solution  

r_S = peak response of albuterol from the Standard solution  

C_S = concentration of USP Albuterol Sulfate RS in the Standard solution (mg/mL)

C_U = nominal concentration of albuterol in the Sample solution (mg/mL)

M = number of moles of albuterol per mole of albuterol sulfate, 2

M_r1 = molecular weight of albuterol, 239.31  

M_r2 = molecular weight of albuterol sulfate, 576.70

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

^a Process impurity is included in the table for identication only. Process impurities are controlled in the drug substance and are not to be reported or included in the total impurities of the drug product.

^b 4-[2-(tert-Butylamino)-1-hydroxyethyl]-2-chloro-6-(hydroxymethyl)phenol.

^c 2-(tert-Butylamino)-1-[3-chloro-4-hydroxy-5-(hydroxymethyl)phenyl]ethanone.

^d 4-{2-[(1,1-Dimethylethyl)amino]-1-hydroxyethyl}-2-methylphenol.

^e 4-[2-(tert-Butylamino)-1-hydroxyethyl]-2-(ethoxymethyl)phenol; also known as α-{[(1,1-Dimethylethyl)amino]methyl}-3-(ethoxymethyl)-4- hydroxy-benzenemethanol.

^f (R)-1-[4-(Benzyloxy)-3-(hydroxymethyl)phenyl]-2-(tert-butylamino)ethan-1-ol; also known as α-{[(1,1-Dimethylethyl)amino]methyl}-4- (phenylmethoxy)-1,3-benzenedimethanol.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Albuterol Sulfate RS

USP Albuterol Related Compound B RS

2-(tert-Butylamino)-1-[4-hydroxy-3-(hydroxymethyl)phenyl]ethanone.

C₁₃H₁₉NO₃  237.29

USP Albuterol Related Compound E RS

2,2′-Oxybis(methylene)bis{4-[2-(tert-butylamino)-1-hydroxyethyl]phenol}diacetate.

C₂₆H₄₀N₂O₅ · 2(C₂H₄O₂) 580.72

USP Levalbuterol Related Compound C RS

4-[2-(tert-Butylamino)-1-hydroxyethyl]-2-(methoxymethyl)phenol;

Also known as α-{[(1,1-Dimethylethyl)amino]methyl}-4-hydroxy-3-(methoxymethyl)-benzenemethanol.

C₁₄H₂₃NO₃ 253.34

USP Levalbuterol Related Compound D RS

5-[2-(tert-Butylamino)-1-hydroxyethyl]-2-hydroxybenzaldehyde sulfate (2:1);

Also known as 5-{2-[(1,1-Dimethylethyl)amino]-1-hydroxyethyl}-2-hydroxy-benzaldehyde sulfate (2:1).

(C₁₃H₁₉NO₃)₂ · H₂SO₄ 572.67

USP Levalbuterol Related Compound H RS

4-[2-(tert-Butylamino)-1-methoxyethyl]-2-(hydroxymethyl)phenol acetate.

C₁₄H₂₃NO₃ · C₂H₄O₂ 313.39 (USP 1-May-2023)