Cromolyn Sodium Oral 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

Cromolyn Sodium Oral Solution is a sterile solution containing NLT 90.0% and NMT 110.0% of the labeled amount of cromolyn sodium (C₂₃H₁₄Na₂O₁₁).

2 IDENTIFICATION

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

B. The retention time 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

Buffer: 10.0 g/L of tetrabutylammonium hydrogen sulfate in water

Mobile phase: Acetonitrile and Buffer (25:75)

Standard solution: 0.2 mg/mL of USP Cromolyn Sodium RS in water

Sample solution: Nominally 0.2 mg/mL of cromolyn sodium from Oral Solution prepared as follows. Mix NLT 5 containers of Oral Solution, transfer a suitable volume of the composite Oral Solution to a suitable volumetric flask, and dilute with water to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 330 nm. For Identification A, use a diode array detector in the range of 220-400 nm.

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cromolyn sodium (C₂₃H₁₄Na₂O₁₁) in the portion of Oral Solution taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of cromolyn sodium from the Sample solution

r_s = peak response of cromolyn sodium from the Standard solution s

C_s = concentration of USP Cromolyn Sodium RS in the Standard solution (mg/mL)

C_u = nominal concentration of cromolyn sodium in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DELIVERABLE VOLUME (698): Meets the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Solution A: 10.0 g/L of tetrabutylammonium hydrogen sulfate in water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (60:40)

System suitability solution: 5 mg/mL of USP Cromolyn Sodium RS and 0.005 mg/mL each of 2-acetylresorcinol, USP Cromolyn Related Compound A RS, and USP Cromolyn Related Compound B RS in Diluent

Sensitivity solution: 0.0025 mg/mL of USP Cromolyn Sodium RS in Diluent

Standard solution: 0.005 mg/mL of USP Cromolyn Sodium RS in Diluent

Sample solution: Nominally 5 mg/mL of cromolyn sodium from Oral Solution prepared as follows. Mix NLT 5 containers of Oral Solution, transfer a suitable volume of the composite Oral Solution to a suitable volumetric flask, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 330 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 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 3.0 between the cromolyn and 2-acetylresorcinol peaks; NLT 3.0 between the cromolyn related compound B and cromolyn related compound A peaks, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oral Solution taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of cromolyn from the Standard solution s

C_s = concentration of USP Cromolyn Sodium RS in the Standard solution (mg/mL)

C_u = nominal concentration of cromolyn sodium in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

a 1-(2,6-Dihydroxyphenyl)ethan-1-one; also known as 2,6-Dihydroxyacetophenone.

6 SPECIFIC TESTS

6.1 STERILITY TESTS (71): Meets the requirements

6.2 PH (791): 4.0-7.0

7 ADDITIONAL REQUIREMENTS

7.1 PACKAGING AND STORAGE:

Preserve in light-resistant containers. temperature.

7.2 LABELING:

The label indicates that the Oral Solution is not to be used if it contains a precipitate or is discolored.

7.3 USP REFERENCE STANDARDS (11)

USP Cromolyn Related Compound A RS

1,3-Bis(2-acetyl-3-hydroxyphenoxy)propan-2-ol.

C₁₉H₂₀O₇       360.36

USP Cromolyn Related Compound B RS

Diethyl 5,5'-[(2-hydroxypropane-1,3-diyl)bis(oxy)]bis (4-oxo-4H-chromene-2-carboxylate).

C₂₇H₂₄O₁₁       524.48

USP Cromolyn Sodium RS (USP 1-Aug-2022)