Azithromycin Capsules

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

Azithromycin Capsules contain the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of azithromycin (C₃₈H₇₂N₂O₁₂).

2 IDENTIFICATION

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

3 ASSAY

3.1 PROCEDURE

[NOTE-Use water that has a resistivity of NLT 18 Mohm-cm.]

Mobile phase: Dissolve 5.8 g of monobasic potassium phosphate in 2130 mL of water, and add 870 mL of acetonitrile. Adjust with about 6 mL of 10 N potassium hydroxide to a pH of 11.0 ± 0.1, and pass through a suitable filter.

Standard stock solution: 0.165 mg/mL of USP Azithromycin RS in acetonitrile. Swirl, and sonicate as necessary.

Standard solution: 3.3 µg/mL of USP Azithromycin RS from the Standard stock solution in Mobile phase

System suitability stock solution: 0.16 mg/mL of USP Azaerythromycin A RS in acetonitrile and Mobile phase (1:9). Dissolve first in acetonitrile, using 10% of the final volume. Swirl, and sonicate to dissolve. Dilute with Mobile phase to volume.

System suitability solution: 3.2 µg/mL of azaerythromycin A from the System suitability stock solution and 3.3 µg/mL of azithromycin from the Standard stock solution in Mobile phase

Sample stock solution: Remove, as completely as possible, the contents of NLT 20 Capsules. Prepare a 1-mg/mL solution of anhydrous azithromycin in acetonitrile. Dissolve a portion of the mixed Capsule contents first in 70% of the final volume of acetonitrile, and shake by mechanical means for 30 min. Dilute with acetonitrile to volume. Place 40 mL of the resulting suspension in a centrifuge tube, and centrifuge. Use the supernatant to prepare the Sample solution.

Sample solution: 3.2 µg/mL of azithromycin from the Sample stock solution in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: Amperometric electrochemical detector

Electrode: Dual glassy carbon electrodes

Mode: Oxidative screen mode

Electrode 1: +0.70 ± 0.05 V

Electrode 2: +0.82 ± 0.05 V

Background current: 85 ± 15 nanoampheres

Columns

Guard: 4.6-mm x 5-cm; 5-µm packing L29

Analytical: 4.6-mm × 15-cm; 5-µm packing L29 or 3-um packing L49 without the guard column

Flow rate: 1.5 mL/min

Injection size: 50 µL

System suitability

Samples: Standard solution and System suitability solution

[NOTE-The relative retention times for azaerythromycin A and azithromycin with the L29 column are 0.7 and 1.0, respectively; the relati retention times for azaerythromycin A and azithromycin with the L49 column are 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.5 between azaerythromycin A and azithromycin, System suitability solution

Column efficiency: NLT 1000 theoretical plates, Standard solution

Tailing factor: 0.9-1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of azithromycin (C₃₈H₇₂N₂O₁₂) in the portion of Capsules taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Azithromycin RS in the Standard solution (µg/mL)

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

P = potency of azithromycin in USP Azithromycin RS (µg/mg)

F = conversion factor, 0.001 mg/µg

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

[NOTE-Use water that has a resistivity of NLT 18 Mohm-cm.]

Medium: pH 6.0 sodium phosphate buffer (Prepare 6 L of 0.1 M dibasic sodium phosphate. Adjust with about 40 mL of hydrochloric acid to a pH of 6.0 ± 0.05, and add 600 mg of trypsin); 900 mL

Apparatus 2: 100 rpm

Time: 45 min

Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard stock solution: 0.3 mg/mL of USP Azithromycin RS in Medium. Sonicate briefly to dissolve.

Standard solution: 3.84 µg/mL of azithromycin from the Standard stock solution in Mobile phase

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.5-µm or finer pore size. Transfer 2.0 mL of the filtrate to a 25-mL volumetric flask, and dilute with Mobile phase to volume. Transfer 4.0 mL of this solution to a second 25-mL volumetric flask, and dilute with Mobile phase to volume.

Analysis

Samples: Standard solution and Sample solution

Determine the amount of azithromycin (C₃₈H₇₂N₂O₁₂) dissolved using the procedure in the Assay, making any necessary modifications.

Calculate the percentage of azithromycin (C₃₈H₇₂N₂O₁₂) dissolved:

Result = (r_U/r_S) × (C_S/L) × D × V × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution s

C_S = concentration of USP Azithromycin RS in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of azithromycin (C₃₈H₇₂N₂O₁₂) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 SPECIFIC TESTS

WATER DETERMINATION, Method (921): NMT 5.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. Where packaged in unit-of-use containers, each container contains six 250-mg Capsules, and the label indicates the intended sequential day of use for each Capsule.

USP REFERENCE STANDARDS (11)

USP Azaerythromycin A RS

USP Azithromycin RS