Cromolyn Sodium Ophthalmic 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 Ophthalmic 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). It may contain suitable antimicrobial and stabilizing agents.

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. Sonication may be needed to aid dissolution.

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

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 x 10-cm; 3.5-µm packing LZ

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)

System suitability

Samples: System suitability solution and Standard solution [NOTE-See Table 1 for the relative retention times.]

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

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_u/r_s) × (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 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 IMPURITIES

Change to read:

4.1 ORGANIC IMPURITIES

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 Ophthalmic Solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 326 nm

Column: 4.6-mm × 10-cm; 3.5-µm packing LZ

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

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.) (USP 1-AUG-2020)

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

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

Analysis

Samples: Standard solution and Sample solution

ug-2020) in the Calculate the percentage of (USP 1-Aug-2020) cromolyn related compound A or cromolyn related compound B (USP 1-Aug-2020) portion of Ophthalmic Solution taken:

Result = (r_u/r_s) × (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 Ophthalmic Solution taken:

Result = (r_u/r_s) × (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

5 SPECIFIC TESTS

5.1 PH (791): 4.0-7.0

5.2 STERILITY TESTS (71): Meets the requirements

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE:

Preserve in tight, light-resistant, single-dose or multiple-dose containers. Ophthalmic Solution that is packaged in multiple-dose containers contains a suitable antimicrobial agent. Store between 15° and 30°.

6.2 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