Albuterol Inhalation Solution

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 Inhalation Solution is an isotonic sterile solution of albuterol sulfate. It may contain chelating agents, isotonicity agents, and pH adjusting agents. It contains NLT 90.0% and NMT 110.0% of the labeled amount of albuterol (C₁₃H₂₁NO₃) as albuterol sulfate.

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. CIAL

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Solution A: 3.4 g/L of monobasic potassium phosphate and 1.1 g/L of sodium 1-heptanesulfonate in water. Adjust with phosphoric acid to a pH of 2.1.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: 0.01 N hydrochloric acid

Standard solution: 0.1 mg/mL of USP Albuterol Sulfate RS (equivalent to 0.08 mg/mL of albuterol) in Diluent

Sample solution: Nominally 0.08 mg/mL of albuterol diluted with Diluent from a suitable volume of Inhalation Solution Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm. For Identication B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 15-cm; 2.6-µm packing L1

Column temperature: 37°

Flow rate: 0.75 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.7

Relative standard deviation: NMT 1.0%

3.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of albuterol (C H NO ) in the portion of Inhalation Solution taken: 13 21 3

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

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

M_r1 = molecular weight of albuterol, 239.31

M_r2 = molecular weight of albuterol sulfate, 576.70

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

5.1 Organic Impurities

Solution A: 3.4 g/L of monobasic potassium phosphate and 1.1 g/L of sodium 1-heptanesulfonate in water. Adjust with phosphoric acid to a pH of 2.1.

Solution B: Acetonitrile

Mobile phase: See Table 2.

Table 2

Diluent: 0.01 N hydrochloric acid

System suitability solution: 0.05 mg/mL each of USP Albuterol Sulfate RS, USP Albuterol Related Compound I RS, and USP Levalbuterol Related Compound H RS in Diluent

Standard solution: 1.25 µg/mL each of USP Albuterol Sulfate RS and USP Levalbuterol Related Compound D RS in Diluent Sample solution: Nominally 200–800 µg/mL of albuterol diluted with Diluent from a suitable volume of Inhalation Solution Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 2.1-mm × 15-cm; 1.7-µm packing L1

Temperatures

Autosampler: 10°

Column: 37°

Flow rate: 0.35 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 3 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between albuterol and albuterol related compound I; NLT 2.0 between albuterol related compound I and levalbuterol related compound H, System suitability solution

Tailing factor: NMT 2.0 for albuterol and levalbuterol related compound D, Standard solution

Relative standard deviation: NMT 5.0% for albuterol and levalbuterol related compound D, Standard solution

Signal-to-noise ratio: NLT 10 for levalbuterol related compound D and albuterol, Standard solution

5.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of levalbuterol related compound D in the portion of Inhalation Solution taken:

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

r_U = peak response of levalbuterol related compound D from the Sample solution

r_S = peak response of levalbuterol related compound D from the Standard solution  

C_S = concentration of USP Levalbuterol Related Compound D RS in the Standard solution (µg/mL)  

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

Calculate the percentage of any individual unspecied degradation product in the portion of Inhalation Solution taken:

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

r_U = peak response of any individual 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 (μg/mL)

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

M_r1 = molecular weight of albuterol, 239.31  

M_r2 = molecular weight of albuterol sulfate, 576.70

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

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

Table 3

^a Process impurity controlled in the drug substance. Not included in total degradation products.

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

^c 4-[2-(tert-Butylamino)ethyl]-2-methylphenol.

^d (1RS)-2-[Benzyl(1,1-dimethylethyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl]ethanol.

^e 2-[Benzyl(1,1-dimethylethyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl]ethanone.

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

^g 1-[4-(Benzyloxy)-3-(hydroxymethyl)phenyl]-2-(tert-butylamino)ethanol.

6 SPECIFIC TESTS

Sterility Tests 〈71〉: Meets the requirements

pH 〈791〉: 3.0–5.0

Particulate Matter in Injections 〈788〉, Method 1 Light Obscuration Particle Count Test

Sample: Pool the contents of NLT 10 units.

Acceptance criteria: See Table 4.

Table 4

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Protect from light. Store in a pouch until the time of use. Store at controlled room temperature. eference Standards 〈11〉

USP Albuterol Related Compound I RS

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

C₁₂H₁₉NO₂   209.28

USP Albuterol Sulfate RS

USP Levalbuterol Related Compound D RS

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

(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 (RB 1-May-2026)