Oseltamivir Phosphate Capsules
DEFINITION
Oseltamivir Phosphate Capsules contain Oseltamivir Phosphate equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of oseltamivir (C16H28N2O4).
IDENTIFICATION
• The retention time of the major peaks of the Sample solution corresponds to those of the Standard solution, as obtained in the Assay.
ASSAY
• Oseltamivir
Solution A:
Dissolve 6.8 g of potassium dihydrogen phosphate in 980 mL of water. Adjust with 1 M potassium hydroxide solution to a pH of 6.0, and dilute with water to 1 L.
Mobile phase:
Methanol, acetonitrile, and Solution A (245:135:620)
Diluent:
Methanol, acetonitrile, and 0.01 N phosphoric acid (245:135:620)
Standard solution:
1 mg/mL of USP Oseltavimir Phosphate RS in Diluent
Sample solution:
Weigh the contents of 20 Capsules, and mix. Prepare the equivalent of about 1 mg of oseltamivir phosphate per mL, based on the label claim, by first dispersing a suitable portion of the powder in about 40% of the flask volume of Diluent using an ultrasonic bath for about 20 min, and diluting with Diluent to volume. Centrifuge an aliquot of this solution, and use the supernatant.
Chromatographic system
Mode:
LC
Detector:
UV 207 nm
Column:
4.6-mm × 25-cm; packing L7
Column temperature:
50
Flow rate:
1.2 mL/min
Injection size:
15 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of oseltamivir (C16H28N2O4) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Oseltamivir Phosphate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of oseltamivir in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of oseltamivir, 312.40 |
| Mr2 | = | = molecular weight of oseltamivir phosphate, 410.40 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Time:
20 min
Detector:
UV 240 nm
Standard solution:
Prepare a solution in Medium having a known concentration of about 0.11 mg/mL of USP Oseltamivir Phosphate RS. Quantitatively dilute a portion of this solution with Medium to obtain a solution having a known concentration similar to the expected concentration in the solution under test.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 1-µm pore size.
Excipients solution:
Suspend an amount of the placebo mixture equivalent to the weight of the excipients in one dosage unit and one empty Capsule shell in 900 mL of Medium. Heat to 37, and filter.
, and filter.
Analysis
Samples:
Medium, Standard solution, Sample solution, and Excipients solution
Determine the amount of oseltamivir phosphate (C16H28N2O4 ·H3PO4) dissolved by measuring the absorbance at about 240 nm of the Sample solution and Excipients solution in comparison with the Standard solution, using the Medium as the blank. Calculate the percentage of oseltamivir phosphate dissolved:
Result = [(AU 
AE) × CS × V × 100]/(AS × L)
AE) × CS × V × 100]/(AS × L)| AU | = | = absorbance of the Sample solution |
| AE | = | = absorbance of the Excipients solution |
| CS | = | = concentration of USP Oseltamivir Phosphate RS in the Standard solution |
| V | = | = volume of Medium, 900 mL |
| AS | = | = absorbance of the Standard solution |
| L | = | = label claim for oseltamivir phosphate (mg/Capsule) |
Tolerances:
NLT 75% (Q) of the labeled amount of oseltamivir phosphate is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Organic Impurities
Solution A, Mobile phase, Diluent, Standard solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of individual impurities in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Oseltamivir Phosphate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of oseltamivir in the Sample solution (mg/mL) |
| F | = | = relative response factor from Table 1 |
| Mr1 | = | = molecular weight of oseltamivir, 312.40 |
| Mr2 | = | = molecular weight of oseltamivir phosphate, 410.40 |
Acceptance criteria:
See Table 1.
Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Impurity Aa | 0.18 | 1.4 | 2.0 |
| Impurity Bb | 0.49 | 2.7 | 0.3 |
| Oseltamivir phosphate |
1.00 | 1.0 | — |
| Impurity Cc | 1.45 | 0.9 | 0.5 |
| Individual unidentified impurity |
— | 1.0 | 0.2 |
| Total unidentified impurities | — | 1.0 | 0.5 |
| Total impurities | — | 1.0 | 3.0 |
|
a
(3R,4R,5S)-4-Acetylamino-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid.
b
4-Acetylamino-3-hydroxybenzoic acid ethyl ester.
c
(3R,4R,5S)-4-Amino-5-acetylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid ethyl ester.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Oseltamivir Phosphate RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Leonel M. Santos, Ph.D.
Senior Scientific Liaison 1-301-816-8168 |
(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 4139
Pharmacopeial Forum: Volume No. 34(6) Page 1471