Ondansetron Orally Disintegrating Tablets
DEFINITION
Ondansetron Orally Disintegrating Tablets contain the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of ondansetron (C18H19N3O).
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.
ASSAY
• Procedure
Diluent:
0.01 N hydrochloric acid
Buffer:
2.72 g/L of monobasic potassium phosphate in water. Adjust with 1 N sodium hydroxide or 0.5 N sodium hydroxide to a pH of 5.4.
Mobile phase:
Acetonitrile and Buffer (48:52)
Standard solution:
40 µg/mL of USP Ondansetron RS in Diluent
System suitability solution:
0.02 mg/mL of USP Ondansetron Related Compound A RS and 0.006 mg/mL of USP Ondansetron RS in Diluent
Sample stock solution:
Equivalent to 400 µg/mL of ondansetron. Transfer 10 Tablets to a suitable volumetric flask. Add Diluent to fill about 60% of the flask capacity. Shake by mechanical means for about 5 min, and dilute with Diluent to volume. Filter a portion of this solution through a polypropylene membrane of 0.45-µm pore size, discarding the first 5 mL of the filtrate.
Sample solution:
40 µg/mL of ondansetron in Diluent, from the Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 216 nm
Column:
4.6-mm × 25-cm; packing L10
Flow rate:
1.5 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times for ondansetron and ondansetron related compound A are 1.0 and 1.1, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between ondansetron related compound A and ondansetron, System suitability solution
Tailing factor:
NMT 2.0 for the ondansetron peak, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of ondansetron (C18H19N3O) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Ondansetron RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of ondansetron in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Disintegration 
701
:
NMT 10 s
701:
NMT 10 s
• Dissolution 711
711
Medium:
0.1 N hydrochloric acid; 500 mL, deaerated
Apparatus 2:
50 rpm
Time:
10 min
Detector:
UV 310 nm
Cell:
1 cm for 4-mg and 8-mg Tablets; 0.5 cm for 16-mg Tablets; 0.2 cm for 24-mg Tablets
Standard solution:
(L/500) mg/mL of USP Ondansetron RS in Medium, where L is the label claim in mg
Sample solution:
Pass a portion of the solution under test through a suitable filter.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ondansetron released:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of USP Ondansetron RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 500 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of C18H19N3O is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Organic Impurities
Buffer:
Prepare as directed in the Assay.
Mobile phase:
Acetonitrile and Buffer (1:4)
Standard solution:
2 µg/mL of USP Ondansetron RS in Mobile phase
System suitability solution:
2 µg/mL each of USP Ondansetron Related Compound D RS, 2-methylimidazole, and USP Ondansetron RS in Mobile phase. [Note—First dissolve in acetonitrile, then dilute with Mobile phase to volume. ]
System sensitivity solution:
0.2 µg/mL of USP Ondansetron RS, from the Standard solution in Mobile phase
Sample solution:
Equivalent to 400 µg/mL of ondansetron. Transfer 10 Tablets to a suitable volumetric flask. Add Mobile phase to fill about 60% of the flask capacity. Shake by mechanical means for about 5 min, and dilute with Mobile phase to volume. Centrifuge a portion of this solution at 3000 rpm for 10 min. Use the supernatant.
Chromatographic system
Mode:
LC
Detector:
UV 216 nm
Column:
4.6-mm × 25-cm; packing L10
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution, System suitability solution, and System sensitivity solution
Suitability requirements
Resolution:
NLT 1.5 between ondansetron and any adjacent peak, System suitability solution
Column efficiency:
NLT 8000 theoretical plates for ondansetron, System suitability solution
Tailing factor:
NMT 2.0 for the ondansetron peak, System suitability solution
Signal-to-noise ratio:
NLT 15, System sensitivity solution
Relative standard deviation:
NMT 5.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak area of any impurity in the Sample solution |
| rS | = | = peak area of ondansetron from the Standard solution |
| CS | = | = concentration of USP Ondansetron RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of the Sample solution (µg/mL) |
| F | = | = relative response factor for each impurity (see Table 1) |
Acceptance criteria:
See Table 1.
[Note—The run time is about 60 min. ]
Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| 2-Methylimidazole | 0.16 | 0.5 | 0.2 |
| Ondansetron related compound D | 0.45 | 1.2 | 0.12 |
| Ondansetron | 1.0 | — | — |
| Individual unknown impurity | — | 1.0 | 0.2 |
| Total impurities | — | — | 0.5 |
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in light-resistant containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Ondansetron RS
USP Ondansetron Related Compound A RS
3[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one.
3[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one.
USP Ondansetron Related Compound D RS 
1,2,3,9-Tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one.
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1,2,3,9-Tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| 701 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| 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 4125
Pharmacopeial Forum: Volume No. 34(6) Page 1467