Naratriptan Tablets
» Naratriptan Tablets contain an amount of Naratriptan Hydrochloride equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of naratriptan (C17H25N3O2S).
Packaging and storage—
Preserve in tight containers, and store at controlled room temperature.
USP Reference standards 
11
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11—
USP Naratriptan Hydrochloride RS 
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USP Naratriptan Resolution Mixture RS
A mixture of naratriptan hydrochloride with approximately 0.1% each of naratriptan related compound A [3-(1-methylpiperidin-4-yl)-1H-indole hydrochloride] and naratriptan related compound B [2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-yl]ethanesulfonic acid methylamide oxalate].
A mixture of naratriptan hydrochloride with approximately 0.1% each of naratriptan related compound A [3-(1-methylpiperidin-4-yl)-1H-indole hydrochloride] and naratriptan related compound B [2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-yl]ethanesulfonic acid methylamide oxalate].
Identification—
A:
Thin-Layer Chromatographic Identification Test 201—
201—
Diluent—
Prepare a mixture of methylene chloride and methanol (1:1).
Adsorbent:
high performance thin-layer chromatographic silica gel.
Test solution—
Transfer a number of Tablets, equivalent to 5 mg of naratriptan, to a 25-mL flask, add 1.0 mL of water to wet the Tablets, and gently shake to remove the Tablet film coating. Add 4.5 mL of Diluent, and shake for 5 minutes or until the Tablets have dispersed. Centrifuge at 3000 rpm for 10 minutes, and pass through a nylon filter having a 0.45-µm porosity.
Developing solvent system:
a mixture of methylene chloride, alcohol, and triethylamine (10:2:1).
B:
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.
Dissolution 711—
711—
Medium:
0.1 N hydrochloric acid; 500 mL, deaerated.
Apparatus 1:
100 rpm.
Times:
15 minutes.
Procedure—
Determine the amount of C17H25N3O2S dissolved from the difference between first derivative absorbance values at the wavelengths of maximum and minimum in the range from 226 nm to 236 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Naratriptan Hydrochloride RS in the same Medium. [note—Do not sonicate the Standard solution to dissolve. Dissolve the USP Reference Standard with Medium at about 37
. ]
. ]
Tolerances—
Not less than 80% (Q) of the labeled amount of C17H25N3O2S is dissolved in 15 minutes.
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Chromatographic purity—
0.05 M Ammonium phosphate buffer and Resolution solution—
Prepare as directed in the test for Chromatographic purity under Naratriptan Hydrochloride.
Solution A—
Use filtered and degassed 0.05 M Ammonium phosphate buffer.
Solution B—
Use filtered and degassed acetonitrile.
Mobile phase—
Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Test solution—
Transfer 5 Tablets into a suitable amber flask. Add 20.0 mL of 0.1 N sodium hydroxide, and allow to stand for 10 minutes. Sonicate for 10 minutes with regular vigorous swirling of the flask. Add 30.0 mL of 0.05 M Ammonium phosphate buffer, and mix well. Centrifuge a portion of this solution at 3500 rpm for about 10 minutes, and pass through a suitable filter having a 0.45-µm porosity, discarding the first 3 mL of the filtrate.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 225-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The column temperature is maintained at 40. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.
Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.07 for 2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide (naratriptan related compound B) and 1.0 for naratriptan; and the resolution, R, between naratriptan and naratriptan related compound B is not less than 1.5.
621)—
The liquid chromatograph is equipped with a 225-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The column temperature is maintained at 40. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.
| Time (minutes) |
Solution A
(%) |
Solution B
(%) |
Elution |
|---|---|---|---|
| 0–35.0 | 97®80 | 3®20 | linear gradient |
| 35.0–40.0 | 80 | 20 | isocratic |
| 40.0–41.0 | 80®97 | 20®3 | linear gradient |
| 41.0–51.0 | 97 | 3 | re-equilibration |
Procedure—
Inject a volume (equivalent to about 5 µg of naratriptan hydrochloride) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for all of the peaks. Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
100(ri /F)/[rN + S(ri /F)]
in which F is the relative response factor (see the accompanying table for values) for each impurity; ri is the peak response for each impurity; and rN is the naratriptan peak response (see the accompanying table for limits). In addition to not exceeding the limits listed in the accompanying table, not more than 0.2% of any other individual impurity is found; and not more than 1.5% of total impurities is found.
| Compound Name | Relative Retention Time |
Relative Response Factor (F) |
Limit (%) |
|---|---|---|---|
| 2-[3-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide | about 1.07 | 0.6 | 0.2 |
| 2,2-Bis-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide | about 1.26 | 0.6 | 0.2 |
| 1-Methyl-4-[5-(2-methylsulfamoyl-ethyl)-1H-indol-3-yl]-pyridinium chloride | about 1.33 | 0.4 | 0.3 |
| 2-[3-(1-methylpiperidin-4-yl)-5-(2-methylsulfamoyl-ethyl)-indol-1-yl]ethanesulfonic acid methylamide | about 1.44 | 0.6 | 0.2 |
| 4-[1,5-Bis-(2-methylsulfamoyl-ethyl)-1H-indol-3-yl]-1-methylpyridinium chloride | about 1.62 | 0.5 | 0.2 |
Assay—
0.01 M Triethylamine phosphate buffer, Mobile phase, and Resolution solution—
Prepare as directed in the Assay under Naratriptan Hydrochloride.
Standard preparation—
Dissolve an accurately weighed quantity of USP Naratriptan Hydrochloride RS in 0.1 N sodium hydroxide to obtain a solution having a known concentration of about 0.2 mg per mL. Dilute an accurately measured volume of this solution in 0.01 M Triethylamine phosphate buffer to obtain a solution having a known concentration of about 20 µg per mL.
Assay preparation—
Transfer 5 Tablets into an amber 250-mL volumetric flask, add 30 mL of 0.1 N sodium hydroxide, and shake on a wrist-action shaker for at least 30 minutes. Sonicate for 10 minutes with regular vigorous swirling of the flask. Add about 170 mL of 0.01 M Triethylamine phosphate buffer, and mix well. Allow to cool to room temperature, dilute with 0.01 M Triethylamine phosphate buffer to volume, and mix. Centrifuge a portion of this solution at 3500 rpm for about 10 minutes, and pass through a suitable filter having a 0.45-µm porosity, discarding the first 3 mL of the filtrate.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 224-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L11. The flow rate is about 1.3 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for 3-(1-methylpiperidin-4-yl)-1H-indole (naratriptan related compound A), 1.0 for naratriptan, and 1.1 for naratriptan related compound B; and the resolution, R, between naratriptan related compound A and naratriptan and between naratriptan related compound B and naratriptan is not less than 1.5. Chromatograph the Standard preparation, record the chromatogram, and measure the peak response as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.5%.
621)—
The liquid chromatograph is equipped with a 224-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L11. The flow rate is about 1.3 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for 3-(1-methylpiperidin-4-yl)-1H-indole (naratriptan related compound A), 1.0 for naratriptan, and 1.1 for naratriptan related compound B; and the resolution, R, between naratriptan related compound A and naratriptan and between naratriptan related compound B and naratriptan is not less than 1.5. Chromatograph the Standard preparation, record the chromatogram, and measure the peak response as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.5%.
Procedure—
Separately inject equal volumes (equivalent to about 1 µg of naratriptan hydrochloride) 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 naratriptan (C17H25N3O2S) in the portion of Tablets taken by the formula:
(335.47/371.93)100(C/D)(rU / rS)
in which 335.47 and 371.93 are the molecular weights of naratriptan and naratriptan hydrochloride, respectively; C is the concentration, in mg per mL, of USP Naratriptan Hydrochloride RS in the Standard preparation; D is the concentration, in mg per mL, of naratriptan in the Assay preparation, based upon the labeled quantity of naratriptan in the portion of Tablets taken and the extent of dilution; 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 | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 4002
Pharmacopeial Forum: Volume No. 30(4) Page 1268