Cromolyn Sodium 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

Cromolyn Sodium Inhalation Solution is a sterile, aqueous solution of Cromolyn Sodium. It contains NLT 90.0% and NMT 110.0% of the labeled amount of cromolyn sodium (C₂₃H₁₄Na₂O₁₁).

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.

Add the following:

B. The UV absorption spectrum of the major peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution, as obtained in the Assay _{▲(USP 1-Aug-2020)}

3 ASSAY

Change to read:

3.1 PROCEDURE

Buffer: 5.6 g/L of monobasic potassium phosphate and 22.2 g/L of myristyltrimethylammonium bromide in water. Adjust with ^▲50% sodium hydroxide TSA _{▲(USP 1-Aug-2020)} to a pH of 6.5.

Mobile phase: Methanol and Buffer (55:45)

Diluent: Acetonitrile and water (30:70)

System suitability solution: 0.5 mg/ml. of USP Cromolyn Sodium RS and 0.02 mg/mL each of USP Cromolyn Related Compound A.RS and USP Cromolyn Related Compound B. RS in Diluent

Standard solution: 0.5 mg/mL of USP Cromolyn Sodium RS in Diluent

Sample solution: Nominally equivalent to 0.5 mg/mL of cromolyn sodium from a volume of Inhalation Solution in Diluent

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 326 nm. ^▲For Identification B, use a diode array detector in the range of 220-400 nm. _{▲(USP 1-Aug-2020)}

Column: 4.6 - mm * 10 - 4 cm; 3.5-µm packing L7

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of cromolyn _{▲(USP 1-Aug-2020)}

3.1.2 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.]

3.1.3 Suitability requirements

Resolution: NLT 2.0 between cromolyn related compound B and cromolyn related compound A; ^▲NLT 2.0 between cromolyn related compound A and cromolyn. _{▲(USP 1-Aug-2020)} System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

3.1.4 Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of cromolyn from the Sample solution

r_S = peak response of cromolyn from the Standard solution 

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

UNIFORMITY OF DOSAGE UNITS (905): Meets the requirements

5 IMPURITIES

Change to read:

6 ORGANIC IMPURITIES

^▲_{▲(USP 1-Aug-2020)} Mobile phase, Diluent, and System suitability solution: Prepare as directed in the Assay.

Standard solution: 0.002 mg/mL each of USP Cromolyn Related Compound A RS, USP Cromolyn Related Compound B RS, and USP Cromolyn Sodium RS in Diluent

Sample solution: Nominally equivalent to 2 mg/mL of cromolyn sodium from a volume of Inhalation Solution in Diluent

3.1.5 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 326 nm

Column: 4.6mm * 10 ^ 4 cm; 3.5-µm packing LZ

3.1.6 Temperatures

Autosampler: 4°

Column: 40°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: ^▲NLTA _{▲(USP 1-Aug-2020)} 2 times the retention time of cromolyn

3.1.7 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.]

3.1.8 Suitability requirements

Resolution: NLT 2.0 between cromolyn related compound B and cromolyn related compound A; NLT 2.0 between cromolyn related compound A and cromolyn, System suitability solution

Relative standard deviation: NMT 3% for 6 replicate injections, Standard solution

3.1.9 Analysis

Samples: Standard solution and Sample solution.

Calculate the percentage of cromolyn related compound A or cromolyn related compound B in the portion of Inhalation Solution taken:

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

r_U = peak response of cromolyn related compound A or cromolyn related compound B from the Sample solution

r_S = peak response of cromolyn related compound A or cromolyn related compound B from the Standard solution

C_S = concentration of ^▲USP Cromolyn Related Compound A RS or USP Cromolyn Related Compound B RSA _{▲(USP 1-Aug-2020)} in the Standard solution (mg/mL)

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

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

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

r_U = peak response of each ^▲individual _{▲(USP 1-Aug-2020}) unspecified degradation product from the Sample solution

r_S = peak response of cromolyn from the Standard solution

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 1.

Table 1

7 SPECIFIC TESTS

PH (791): 4.0-7.0

STERILITY TESTS (71): Meets the requirements

8 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in single-unit double-ended glass ampuls or in low-density polyethylene ampuls. Store at controlled room temperature, protected from light.

LABELING: The label indicates that the Inhalation Solution is not to be used if it contains a precipitate.

USP REFERENCE STANDARDS (11)

USP Cromolvn 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