Sumatriptan 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

Sumatriptan Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of sumatriptan (C₁₄H₂₁N₃O₂S).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K. (CN 1-May-2020) The IR spectrum exhibits main bands at or near (±1) wavenumbers (cm−1) 1708, 1567, 1339, 1300, 1235, 1207, 989, and 844.

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

Buffer solution A: 2.9 g/L of monobasic sodium phosphate, 1.3 mL/L of dibutylamine, and 0.4 mL/L of phosphoric acid in water. Adjust with 10 N sodium hydroxide to a pH of 6.5.

Buffer solution B: 3.9 g/L of monobasic sodium phosphate. Adjust with 10 N sodium hydroxide to a pH of 6.5 before dilution.

Mobile phase: Acetonitrile and Buffer solution A (1:3)

Diluent: Acetonitrile and Buffer solution B (1:3)

Standard solution: Equivalent to 0.1 mg/mL of sumatriptan from USP Sumatriptan Succinate RS in Diluent

Sample stock solution: Nominally 1–2 mg/mL of sumatriptan from NLT 5 Tablets prepared as follows. Transfer the Tablets to a suitable volumetric flask. Add Diluent to fill 60%–80% of the flask volume. Sonicate for 15–20 min with intermittent shaking. Dilute with Diluent to volume.

Sample solution: Nominally 0.1 mg/mL of sumatriptan in Diluent from the Sample stock solution. Pass through a suitable fIlter of 0.45-μm pore size.

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

Run time: NLT 1.7 times the retention time of sumatriptan

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

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

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

M_r1 = molecular weight of sumatriptan, 295.4

M_r2 = molecular weight of sumatriptan succinate, 413.5

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 30 rpm

Time: 15 min

Standard solution: 0.025 mg/mL of USP Sumatriptan Succinate RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable fIlter of 0.45-μm pore size. Dilute with Medium if necessary.

Instrumental conditions

Mode: UV

Detector: about 282 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sumatriptan (C₁₄H₂₁N₃O₂S) dissolved:

Result = (A_U/A_S) × C_S × V × D × (M_r1/M_r2) × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor

M_r1 = molecular weight of sumatriptan, 295.4

M_r2 = molecular weight of sumatriptan succinate, 413.5

L = label claim (mg/Tablet)

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

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Standard solution: (L/900) mg/mL of USP Sumatriptan Succinate RS in Medium, where L is the Tablet label claim in mg

Sample solution: Pass a portion of the solution under test through a suitable fIlter of 0.45-μm pore size.

Instrumental conditions

Mode: UV

Detector: About 282 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sumatriptan (C₁₄H₂₁N₃O₂S) dissolved:

Result = (A_U/A_S) × C_S × V × (M_r1/M_r2) × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

M_r1 = molecular weight of sumatriptan, 295.4

M_r2 = molecular weight of sumatriptan succinate, 413.5

L = label claim (mg/Tablet)

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

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: 0.035 mg/mL of USP Sumatriptan Succinate RS in Medium

Sample solution: Dilute the solution if necessary and pass a portion of the solution under test through a suitable fIlter of 0.45-μm pore size.

Instrumental conditions

Mode: UV

Detector: About 283 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sumatriptan (C₁₄H₂₁N₃O₂S) dissolved:

Result = (A_U/A_S) × C_S × V × D × (M_r1/M_r2) × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor

M_r1 = molecular weight of sumatriptan, 295.4

M_r2 = molecular weight of sumatriptan succinate, 413.5

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of sumatriptan is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Diluent: 0.1 N hydrochloric acid

Buffer: 1.9 g/L of ammonium acetate. Adjust with acetic acid to a pH of 4.1.

Solution A: Acetonitrile and methanol (90:10)

Solution B: Solution A and Buffer (5:95)

Solution C: Solution A and Buffer (22:78)

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.1 mg/mL each of USP Sumatriptan Succinate RS and USP Sumatriptan Succinate Related Compound C RS in Diluent

Sensitivity solution: 0.7 μg/mL of USP Sumatriptan Succinate Related Compound C RS in Diluent

Sample solution: Nominally 1.25 mg/mL of sumatriptan from NLT 5 Tablets in Diluent prepared as follows. Transfer the Tablets to a suitable volumetric flask. Add Diluent to fill 80% of the flask volume. Sonicate for 5 min to disperse the Tablets completely. Allow to cool to room temperature for NLT 15 min. Dilute with Diluent to volume. Centrifuge a portion of the solution at NLT 3000 RM for 10 min. Alternatively, the

Sample solution may be fIltered using a suitable fIlter. Use the supernatant or filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 282 nm

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

Column temperature: 50°

Flow rate: 2 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Sensitivity solution

Suitability requirements

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

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of each impurity as well as any individual unspecified degradation product in the portion of Tablets taken:

Result = (r_U/r_T) × (1/F) × 100

r_U = peak response for each impurity from the Sample solution

r_T = sum of peak responses for all peaks in the Sample solution

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 1-{3-[2-(Dimethylamino)ethyl]-3-hydroxy-2-oxoindolin-5-yl}-N-methylmethanesulfonamide.

^b [3-[2-Aminoethyl)]-1H-indol-5-yl]-N-methylmethanesulfonamide.

^c Process impurity, included for peak identification purposes only, controlled in the drug substance.

^d N-Methyl-1-{3-[2-(methylamino)ethyl]-1H-indol-5-yl}methanesulfonamide.

^e N-Methyl-1-{3-[2-(dimethylamino N-oxide)ethyl]-1H-indol-5-yl}methanesulfonamide.

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

^g {3-[2-(Dimethylamino)ethyl]-1-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methyl)-1H-indol-5-yl}-N-methylmethanesulfonamide.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store between 2° and 30°.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Sumatriptan Succinate RS

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