Azithromycin Capsules
DEFINITION
Azithromycin Capsules contain the equivalent of 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.
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
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 × 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
Calculate the percentage of the labeled amount of azithromycin (C38H72N2O12) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × P × F × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Azithromycin RS in the Standard solution (µg/mL) |
| CU | = | = 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%
PERFORMANCE TESTS
• Dissolution 
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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 = (rU/rS) × (CS/L) × D × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = 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.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
SPECIFIC TESTS
• Water Determination, Method I 921:
NMT 5.0%
921:
NMT 5.0%
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.
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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 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2283
Pharmacopeial Forum: Volume No. 27(6) Page 3394