Sumatriptan

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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C₁₄H₂₁N₃O₂S 295.40

1H-Indole-5-methanesulfonamide, 3-[2-(dimethylamino) ethyl]-N-methyl-;

3-[2-(Dimethylamino)ethyl]-N-methyl-1H-indole-5- methanesulfonamide CAS RN®: 103628-46-2; UNII: 8R78F6L9VO.

1 DEFINITION

Sumatriptan contains NLT 98.0% and NMT 102.0% of sumatriptan (C₁₄H₂₁N₃O₂S), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

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

3 ASSAY

Procedure

Diluent: Dissolve 3.9 g of monobasic sodium phosphate dihydrate in water. Adjust with a solution of 50% (w/v) sodium hydroxide to a pH of about 6.5, and dilute with water to 1 L. Mix 750 mL of the this solution with 250 mL of acetonitrile.

Buffer: Dissolve 1.7 mL of dibutylamine, 0.6 mL of phosphoric acid, and 3.9 g of monobasic sodium phosphate dihydrate in water. Adjust with a solution of 50% (w/v) sodium hydroxide to a pH of about 6.5, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (25:75)

System suitability solution: 0.28 mg/mL of USP Sumatriptan Succinate RS and 0.14 mg/mL of USP Sumatriptan Succinate Related

Compound C RS in Diluent

Standard solution: 0.14 mg/mL of USP Sumatriptan Succinate RS in Diluent

Sample solution: 0.1 mg/mL of Sumatriptan in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 282 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for sumatriptan succinate related compound C and sumatriptan are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between sumatriptan succinate related compound C and sumatriptan, System suitability solution

Relative standard deviation: NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sumatriptan (C₁₄H₂₁N₃O₂S) in the portion of the sample 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 Sumatriptan Succinate RS in the Standard solution (mg/mL)

C_U = concentration of Sumatriptan in the Sample solution (mg/mL)

M_r1 = molecular weight of sumatriptan, 295.4

M_r2 = molecular weight of sumatriptan succinate, 413.5

Acceptance criteria: 98.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Procedure 1: Limit of Sumatriptan Related Compound A

Buffer: Dissolve 77.1 g of ammonium acetate in 100 mL of water.

Mobile phase: Methanol and Buffer (90:10)

Standard solution: 6.25 μg/mL of USP Sumatriptan Succinate Related Compound A RS in Mobile phase

Sample solution: 2 mg/mL of Sumatriptan in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 282 nm

Column: 4.6-mm × 25-cm; 5-μm packing L3

Flow rate: 2 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sumatriptan related compound A in the portion of Sumatriptan 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 Sumatriptan Succinate Related Compound A RS in the Standard solution (mg/mL)

C_U = concentration of Sumatriptan in the Sample solution (mg/mL)

M_r1 = molecular weight of sumatriptan related compound A, 495.7

M_r2 = molecular weight of sumatriptan succinate related compound A, 613.8

Acceptance criteria: NMT 0.6%

Procedure 2

Diluent and System suitability solution: Prepare as directed in the Assay.

Buffer: Dissolve 1.7 mL of dibutylamine, 0.6 mL of phosphoric acid, and 3.9 g of monobasic sodium phosphate dihydrate in water. Adjust with a solution of 50% (w/v) sodium hydroxide to a pH of about 7.5, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (25:75)

Identification solution: 3 mg/mL of USP Sumatriptan Succinate Related Impurities RS in Mobile phase

Sample solution: 2 mg/mL of Sumatriptan in Diluent

Chromatographic system: Prepare as directed in the Assay. After making sure that the resolution criteria are met, chromatograph the

Identification solution, and record the peak responses as directed in the Analysis. Identify the peaks according to Table 1.

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.5 between sumatriptan succinate related compound C and sumatriptan

Analysis

Sample: Sample solution

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

Result = (r_U/r_T) × 100

r_U = peak response for each impurity

r_T = sum of all the peak responses

Acceptance criteria: See Table 1.

Table 1

^a Includes the amount of sumatriptan related compound A determined in the test for Limit of Sumatriptan Related Compound A.

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Protect from freezing, and store below 30°.

Change to read:

USP Reference Standards 〈11〉

USP Sumatriptan RS

USP Sumatriptan Succinate RS

USP Sumatriptan Succinate Related Compound A RS

[3-[2-(Dimethylamino)ethyl]-2-[[3-[2-(dimethylamino) ethyl]-1H-indol-5-yl]methyl]-1H-indol-5-yl]-N-methylmethanesulfonamide succinate salt.

C₁₄H₂₁N₃O₂S · C₄H₆O₄ 613.77

USP Sumatriptan Succinate Related Compound C RS

[3-[2-(Dimethylamino)ethyl]-1-(hydroxymethyl)-1H-indol-5-yl]-N-methylmethanesulfonamide succinate salt.

C₁₅H₂₃N₃O₃S · 0.5C₄H₆O₄ 384.47

USP Sumatriptan Succinate Related Impurities RS

Mixture of sumatriptan succinate, [3-[2-(methylamino)ethyl]-1H-indol-5-yl]-N-methylmethanesulfonamide, (ERR 1-Jun-2019) sumatriptan succinate related compound C, [3-[2-(dimethylamino-N-oxide)ethyl]-1H-indol- 5-yl]-N-methylmethanesulfonamide, and [3-[2-(aminoethyl)]-1H- indol-5-yl]-N-methyl methanesulfonamide.