Ondansetron Injection
» Ondansetron Injection is a sterile solution of Ondansetron Hydrochloride in Water for Injection or of Ondansetron in Water for Injection prepared with the aid of Hydrochloric Acid. It may contain suitable buffers and/or tonicity adjusting agents. It contains an amount of Ondansetron Hydrochloride equivalent to not less than 95.0 percent and not more than 105.0 percent of the labeled amount of ondansetron (C18H19N3O).
Packaging and storage—
Preserve in single-dose or in multiple-dose containers, preferably of Type I glass, at a temperature between 2
and 30, protected from light.
and 30, protected from light.
USP Reference standards 
11
—
11—
USP Endotoxin RS
USP Ondansetron Hydrochloride RS 
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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 B RS
6,6¢-Methylene bis-[(1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)-methyl]-4H-carbazol-4-one.
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6,6¢-Methylene bis-[(1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)-methyl]-4H-carbazol-4-one.
USP Ondansetron Related Compound C RS
1,2,3,9-Tetrahydro-9-methyl-4H-carbazol-4-one.
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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.
Identification—
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Bacterial endotoxins 85—
It contains not more than 9.9 USP Endotoxin Units per mg of ondansetron hydrochloride.
85—
It contains not more than 9.9 USP Endotoxin Units per mg of ondansetron hydrochloride.
pH 791:
between 3.3 and 4.0.
791:
between 3.3 and 4.0.
Particulate matter 788:
meets the requirements for small-volume injections.
788:
meets the requirements for small-volume injections.
Limit of ondansetron related compound D—
Mobile phase, Standard solution, System suitability solution, and Chromatographic system—
Proceed as directed in the test for Limit of ondansetron related compound D under Ondansetron Hydrochloride.
Test solution—
Transfer an accurately measured volume of Injection, equivalent to about 10 mg of ondansetron, to a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity of ondansetron related compound D in the volume of Injection taken by the formula:
(2.5 / V)(CS / CA)(rU / rS)
in which V is the volume, in mL, of Injection taken; CS is the concentration, in µg per mL, of ondansetron related compound D in the Standard preparation; CA is the concentration, in mg per mL, of ondansetron in the Injection, as determined in the Assay; and rU and rS are the peak responses obtained from the Test preparation and the Standard preparation, respectively: not more than 0.12% is found.
Chromatographic purity—
Mobile phase and Chromatographic system—
Proceed as directed in the Assay.
System suitability solution—
Use the System suitability solution prepared as directed in the test for Limit of ondansetron related compound D under Ondansetron Hydrochloride.
Test solution—
Use the Assay preparation.
Procedure—
Inject about 20 µL of the System suitability solution, record the chromatogram, and identify the peaks due to ondansetron related compound C and ondansetron related compound D based on their approximate relative retention times of 0.35 and 0.37, respectively. Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. [note—Ignore the peak due to ondansetron related compound D. ] Calculate the percentage of each impurity in the volume of Injection taken by the formula:
100(ri / rs)
in which ri is the peak response for each impurity; and rs is the sum of the responses of all of the peaks: not more than 0.2% of any individual impurity is found, and the total of all impurities, including the percentage of ondansetron related compound D determined in the test for Limit of ondansetron related compound D, is not more than 0.5%.
Other requirements—
It meets the requirements under Injections 1.
1.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of 0.02 M monobasic potassium phosphate (previously adjusted with 1 M sodium hydroxide to a pH of 5.4), and acetonitrile (50:50). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Dissolve an accurately weighed quantity of USP Ondansetron Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.1 mg per mL.
System suitability solution—
Dissolve suitable quantities of USP Ondansetron Hydrochloride RS and USP Ondansetron Related Compound A RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution containing about 0.1 mg per mL and 50 µg per mL, respectively.
Assay preparation—
Transfer an accurately measured volume of Injection, equivalent to about 2 mg of ondansetron, to a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 216-nm detector and a 4.6-mm × 20-cm column that contains packing L10. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for ondansetron and 1.1 for ondansetron related compound A; and the resolution, R, between ondansetron related compound A and ondansetron is not less than 1.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 1.5%.
621)—
The liquid chromatograph is equipped with a 216-nm detector and a 4.6-mm × 20-cm column that contains packing L10. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for ondansetron and 1.1 for ondansetron related compound A; and the resolution, R, between ondansetron related compound A and ondansetron is not less than 1.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of ondansetron (C18H19N3O) in each mL of the Injection taken by the formula:
(293.36 / 329.82)(25C / V)(rU / rS)
in which 293.36 and 329.82 are the molecular weights of ondansetron and anhydrous ondansetron hydrochloride, respectively; C is the concentration, in mg per mL, on the anhydrous basis, of USP Ondansetron Hydrochloride RS in the Standard preparation; V is the volume, in mL, of Injection taken; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
USP35–NF30 Page 4120
Pharmacopeial Forum: Volume No. 32(4) Page 1096