Azithromycin for Oral Suspension
DEFINITION
Azithromycin for Oral Suspension is a dry mixture of Azithromycin and one or more buffers, sweeteners, diluents, anticaking agents, and flavors. It contains NLT 90.0% and NMT 110.0% of the labeled amount of azithromycin (C38H72N2O12).
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.
ASSAY
• 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.
Diluent:
Dissolve 2.2 g of monobasic potassium phosphate in 1590 mL of water, and add 600 mL of isopropyl alcohol, 480 mL of alcohol, and 330 mL of acetonitrile. Adjust with 10 N potassium hydroxide to a pH of 8.4 ± 0.1, and shake by mechanical means for 30 min.
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 1 (where packaged in a single-unit container):
2 mg/mL of azithromycin from Azithromycin for Oral Suspension in Diluent. Transfer the contents of a container of Azithromycin for Oral Suspension to a suitable volumetric flask. Add Diluent equal to 70% of the volume of the flask, and shake by mechanical means for 30 min. Dilute with Diluent to volume. Transfer 40 mL of this suspension to a stoppered centrifuge tube, and centrifuge for 20 min. Use the supernatant to prepare Sample solution 1.
Sample stock solution 2 (where packaged in a multiple-unit container):
0.4 mg/mL of azithromycin from Azithromycin for Oral Suspension in Diluent. Constitute Azithromycin for Oral Suspension as directed in the labeling. Transfer a suitable aliquot of the suspension so obtained, freshly mixed and free from air bubbles to a suitable volumetric flask to obtain to obtain a final concentration of 0.4 mg/mL. Add Diluent equal to 70% of the final volume, shake by mechanical means for 30 min, and dilute with Diluent to volume. Transfer 40 mL of the suspension so obtained to a stoppered centrifuge tube, and centrifuge for 20 min. Use the supernatant to prepare Sample solution 2.
Sample solution 1:
3.2 µg/mL of azithromycin from Sample stock solution 1 in Mobile phase
Sample solution 2:
4 µg/mL of azithromycin from Sample stock solution 2 in Mobile phase
Chromatographic system
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 nanoamperes
Column
Guard:
4.6-mm × 5-cm; 5-µm packing L29
Analytical:
4.6-mm × 15-cm; 5-µm packing L29 or 3-µm 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 relative 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
Where packaged in a single-unit container
Calculate the percentage of the labeled amount of azithromycin (C38H72N2O12) in the portion of Azithromycin for Oral Suspension taken:
Result = (rU/rS) × (CS/CU) × P × F × 100
| rU | = | = peak response from Sample solution 1 |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Azithromycin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of azithromycin in Sample solution 1 (mg/mL) |
| P | = | = potency of azithromycin in USP Azithromycin RS (µg/mg) |
| F | = | = conversion factor, 0.001 mg/µg |
Where packaged in a multiple-unit container
Calculate the percentage of the labeled amount of azithromycin (C38H72N2O12) in the portion of Azithromycin for Oral Suspension taken:
Result = (rU/rS) × (CS/CU) × P × F × 100
| rU | = | = peak response from Sample solution 2 |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Azithromycin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of azithromycin in Sample solution 2 (mg/mL) |
| P | = | = potency of azithromycin in USP Azithromycin RS (µg/mg) |
| F | = | = conversion factor, 0.001 mg/µg |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Deliverable Volume 
698
:
Meets the requirements
698:
Meets the requirements
• Uniformity of Dosage Units 905:
Meets the requirements for a solid packaged in single-unit containers
905:
Meets the requirements for a solid packaged in single-unit containers
SPECIFIC TESTS
• pH 791
791
For a solid packaged in single-unit containers:
9.0–11.0, in the suspension constituted as directed in the labeling
For a solid packaged in multiple-unit containers:
8.5–11.0, in the suspension constituted as directed in the labeling
• Water Determination, Method I 921:
NMT 1.5%
921:
NMT 1.5%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers.
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ahalya Wise, M.S.
Senior Scientific Liaison 1-301-816-8161 |
(SM12010) Monographs - Small Molecules 1 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2286