Cromolyn Sodium Nasal 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 

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Cromolyn Sodium Nasal Solution is an 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. _{▲(USP 1-Aug-2020)} 

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.

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. 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

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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 Nasal 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 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)}

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, 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 Nasal Solution taken: 2

                 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 IMPURITIES

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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 Nasal Solution in Diluent

4.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 326 nm

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

4.1.2 Temperatures

Autosampler: 4°

Column: 40°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

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

4.1.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.) _{▲(USP 1-Aug-2020)}

4.1.4 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 for each peak, Standard solution

4.1.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cromolyn related compound A or cromolyn related compound B in the portion of Nasal 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 RS _{▲(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 Nasal 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

5 SPECIFIC TESTS

PH (791): 4.0-7.0

PH (791): 4.0-7.0
Add the following:
MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): The total aerobic microbial count is NMT 10² cfu/mL, and the total combined molds and yeasts count is NMT 10¹ cfu/mL. It meets the requirements of the tests for absence of Staphylococcus aureus and Pseudomonas aeruginosa _{▲(USP 1-Aug-2020)}

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature.

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