Naratriptan Hydrochloride

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

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

DOWNLOAD PDF HERE

C₁₇H₂₅N₃O₂S · HCl             371.93

1H-Indole-5-ethanesulfonamide, N-methyl-3-(1-methyl-4-piperidinyl)-, monohydrochloride;

N-Methyl-3-(1-methyl-4-piperidyl)indole-5-ethanesulfonamide monohydrochloride CAS RN^®: 143388-64-1; UNII: 10X8X4P12Z.

Change to read:

1 DEFINITION

Naratriptan Hydrochloride contains NLT 98.0% and NMT 101.0% of naratriptan hydrochloride (C₁₇H₂₅N₃O₂S · HCl), calculated on the anhydrous and solvent-free basis. 

^▲_{▲(USP 1-May-2021)}

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Delete the following:

^▲ C. IDENTIFICATION TESTS-GENERAL (191), Chloride: It meets the requirements of test C. _{▲(USP 1-May-2021)}

Add the following:

^▲C. CHLORIDE

CAUTION-This test evolves chlorine gas.]

Sample: Mix the solid under test with an equal weight of manganese dioxide and moisten with sulfuric acid.

Analysis: Gently heat the Sample, while exposing moistened starch iodide paper to the evolving gas.

Acceptance criteria: A gas evolves producing a blue color on the paper. _{▲(USP 1-May-2021)}

3 ASSAY

Change to read:

PROCEDURE

^▲[NOTE-Store the System suitability solution, Standard solution, and Sample solution in a cool place, protected from light. _{▲(USP 1-May-2021)}

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

Mobile phase: Isopropyl alcohol and Solution A (1:9)

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

Standard solution: 0.11 mg/ml. of USP Naratriptan Hydrochloride RS in Mobile phase

Sample solution: 0.11 mg/mL of Naratriptan Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 282 nm

Column: 4.6-mm x 15-cm; 3-µm packing L11

Column temperature: 35°

Flow rate: 1.5 mL/min.

Injection volume: 10 µL

^▲Run time: NLT 2 times the retention time of naratriptan _{▲(USP 1-May-2021)}

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for 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 the naratriptan related compound A and naratriptan peaks; NLT 1.5 between the naratriptan and naratriptan related compound B peaks, System suitability solution

Relative standard deviation: ^▲NMT 0.73%, _{▲(USP 1-May-2021)} Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of naratriptan hydrochloride (C₁₇H₂₅N₃O₂S · HCl) in the portion of Naratriptan Hydrochloride taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 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 = concentration of Naratriptan Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-101.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Change to read:

ORGANIC IMPURITIES

▲[NOTE-Store the System suitability solution and Sample solution in a cool place, protected from light.) _{▲(USP 1-May-2021)}

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

Solution A: Acetonitrile and Buffer (3:97)

Solution B: Acetonitrile and Buffer (20:80)

Mobile phase: See Table 1.

Table 1

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

Sample solution: 0.11 mg/mL of Naratriptan Hydrochloride in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm x 15-cm; 4-µm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 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 any individual impurity in the portion of Naratriptan Hydrochloride 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 (see Table 2)

r_N = peak response of naratriptan from the Sample solution

Acceptance criteria: See Table 2.

Table 2

^a N-Methyl-2,2-bis[3-(1-methylpiperidin-4yl)-1H-indol-5-yl)ethanesulfonamide; Also known as 2,2-Bis-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide.

^b 1-Methyl-4-(5-[2-(N-methylsulfamoyl)ethyl]-1H-indol-3-yl)pyridin-1-ium; Also known as 1-Methyl-4-[5-(2-methylsulfamoyl-ethyl)-1H-indol-3-yl]-pyridinium.

^c 2,2'-[3-(1-Methylpiperidin-4-yl)-1H-indole-1,5-diyl)bis(N-methylethanesulfonamide); Also known as 2-(3-(1-Methylpiperidin-4-yl)-5-(2-methylsulfamoyl-ethyl)-indol-1-yl]ethanesulfonic acid methylamide.

^d 4-[1,5-Bis(2-(N-methylsulfamoyl)ethyl)-1H-indol-3-yl]-1-methylpyridin-1-ium; Also known as 4-[1,5-Bis-(2-methylsulfamoyl-ethyl)-1H-indol-3-yl]-1-methylpyridinium.

^e N-Methyl-2-13-(1-methylpiperidin-4-yl)-1H-indol-5-yl]-N-[2-(N-methylsulfamoyl)ethyl]ethanesulfonamide; Also known as 2-[3-(1-Methylpiperidin-4-yl)-1H-indol-5-yl]ethane-sulfonic acid methyl-(2-methylsulfamoyl-ethyl)amide.

^f 5-Ethyl-3-(1-methylpiperidin-4-yl)-1H-indole.

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method : NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store below 30".

USP REFERENCE STANDARDS (11)

USP Naratriptan Hydrochloride RS

USP Naratriptan Resolution Mixture RS

Contains a mixture of Naratriptan Hydrochloride with approximately 0.1% each of the following compounds:

Naratriptan related compound A: [3-(1-Methylpiperidin-4-yl)-1H-indole hydrochloride].

Naratriptan related compound B: [2-[3-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]ethanesulfonic acid methylamide oxalate].