Naratriptan Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Naratriptan Tablets contain an amount of Naratriptan Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of naratriptan (C₁₇H₃₅N₃O₂S)

2 IDENTIFICATION

Delete the following:

A. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Diluent: Methylene chloride and methanol (1:1)

Standard solution: 1.0 mg/mL of USP Naratriptan Hydrochloride RS prepared as follows. Transfer 5.5 mg of USP Naratriptan Hydrochloride RS to a 25-mL flask, add 1 mL of water and gently shake. Add 4.5 mL of Diluent, and shake for 5 min. Centrifuge at 3000 rpm for 10 min, and pass through a suitable filter of a 0.45-µm pore size.

Sample 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 min or until the Tablets have dispersed. Centrifuge at 3000 rpm for 10 min, and pass through a suitable filter of a 0.45-um pore size.

Chromatographic system

(See Chromatography (621) General Procedures. Thin-Layer Chromatography)

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Developing solvent system: Methylene chloride, alcohol, and triethylamine (10:2:1)

Analysis

Sample: Standard solution and Sample solution

Acceptance criteria: The R, value of the principal spot of the Sample solution corresponds to that of the Standard solution. _2S (USP41)

Change to read:

A_{2S (USP41)} The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. _2S(USP41)

3 ASSAY

Change to read:

PROCEDURE

Solution A: Dilute 0.6 mL of phosphoric acid with water to 900 mL, and adjust with triethylamine to a pH of 2.5.

Mobile phase: Isopropyl alcohol and Solution A (10:90)

System suitability solution: 0.7 mg/mL of USP Naratriptan Resolution Mixture RS in Mobile phase

Standard stock solution: 0.2 mg/mL of USP Naratriptan Hydrochloride RS in 0.1 N sodium hydroxide

Standard solution: 0.02 mg/mL of USP Naratriptan Hydrochloride RS in Solution A from Standard stock solution

Sample solution: Nominally (L/50) mg/mL of naratriptan, where L is the label claim in mg/Tablet, prepared as follows. 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 min. Sonicate for 10 min with regular vigorous swirling of the flask. Add about 170 mL of Solution A. Allow to cool to room temperature and dilute with Solution A to volume. Centrifuge a portion of this solution at 3500 rpm for about 10 min, and pass through a suitable filter of 0.45-µm pore size, discarding the first 3 mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 224 nm. For Identification B, use a diode array detector in the range of 200-400 nm._{2S (USP41)}

Column: 4.6-mm x 15-cm; 5-um packing L11

Flow rate: 1.3 mL/min

Injection volumes

System suitability solution: 10 µL

Standard solution: 50 µL

Tablets labeled to contain 1 mg of naratriptan: 50 µL

Tablets labeled to contain 2.5 mg of naratriptan: 20 µL

Run time: NLT 1.5 times of the retention time of naratriptan _{2S (USP41)}

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for 3-(1-methylpiperidin-4-yl)-1H-indole (naratriptan related compound A), naratriptan, and naratriptan related compound B are 0.9, 1.0, and 1.1, respectively.]

Suitability requirements

Resolution: NLT 1.5 between naratriptan related compound A and naratriptan and between naratriptan related compound B and naratriptan, System suitability solution

Relative standard deviation: NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of naratriptan (C₁₇H₃₅N₃O₂S) in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Naratriptan Hydrochloride RS in the Standard solution (mg/mL)

C_u = nominal concentration of naratriptan in the Sample solution (mg/mL)

M_r1 = molecular weight of naratriptan, 335.47

M_r2 = molecular weight of naratriptan hydrochloride, 371.93

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 500 mL, deaerated

Apparatus 1: 100 rpm

Time: 15 min

Standard solution: USP Naratriptan Hydrochloride RS in Medium

[NOTE-Do not sonicate the Standard solution to dissolve. Dissolve USP Naratriptan Hydrochloride RS with Medium at about 37^o.]

Sample solution: Filter portions of the solution under test and dilute with Medium, if necessary.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)_2S (USP41)

Mode: UV

Analytical wavelength: 226-236 nm

Analysis

Samples: Standard solution and Sample solution

Determine the labeled amount of naratriptan (C₁₇H₃₅N₃O₂S) dissolved from the difference between the first derivative absorbance values at the wavelengths of maximum and minimum in the range from 226 to 236 nm on the Sample solution, suitably diluted with Medium, if necessary, in comparison with the Standard solution.

Tolerances: NLT 80% (Q) of the labeled amount of naratriptan (C₁₇H₃₅N₃O₂S) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A: 5.75 g/L of monobasic ammonium phosphate in water. Adjust with phosphoric acid to a pH of 3.00 ± 0.05.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.11 mg/mL of USP Naratriptan Resolution Mixture RS

Sample solution: Nominally (L/10) mg/mL of naratriptan, where L is the label claim in mg/Tablet, prepared as follows. Transfer 5 Tablets into a suitable amber flask. Add 20.0 mL of 0.1 N sodium hydroxide, and allow to stand for 10 min. Sonicate for 10 min with regular vigorous swirling of the flask. Add 30.0 mL of Solution A, and mix well. Centrifuge a portion of this solution at 3500 rpm for about 10 min and pass through a suitable filter of 0.45-µm pore size, discarding the first 3 ml. of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm x 15-cm; 4-µm 25 (USP41) packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volumes

System suitability solution: 50 μL

Tablets labeled to contain 1 mg of naratriptan: 50 μL

Tablets labeled to contain 2.5 mg of naratriptan: 20 µL

System suitability

Sample: System suitability solution

[NOTE-See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between naratriptan and naratriptan related compound B

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_U /F)/[r_N + Σ(r_U /F)] × 100

r_U = peak response of each impurity from the Sample solution

F = relative response factor for each impurity (see Table 2)

r_N = peak response of naratriptan from the Sample solution

Acceptance criteria: See Table 2.

Table 2

^a 2-[3-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide oxalate.

^b 2,2-Bis-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide.

^c 1-Methyl-4-[5-(2-methylsulfamoyl-ethyl)-1H-indol-3-yl]-pyridinium chloride.

^d 2-[3-(1-Methylpiperidin-4-yl)-5-(2-methylsulfamoyl-ethyl)-indol-1-yl]ethanesulfonic acid methylamide.

^e 4-[1,5-Bis-(2-methylsulfamoyl-ethyl)-1H-indol-3-yl]-1-methylpyridinium chloride.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Naratriptan Hydrochloride RS

USP Naratriptan Resolution Micture 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]