Sumatriptan Nasal Spray

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 Nasal Spray is an aqueous, buffered solution of Sumatriptan. It is supplied in a form suitable for nasal administration. It contains NLT 90.0% and NMT 110.0% of the labeled amount of sumatriptan (C₁₄H₂₁N₃O₂S).

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy : 197M (CN 1-M  -2020)

Sample: To the contents of one vial of Nasal Spray add 1 mL of a saturated sodium chloride solution. Add 1 mL of a saturated solution of sodium carbonate, and shake vigorously for about 30 s. To the solution so obtained add 2 mL of isopropyl alcohol, shake vigorously for about 30 s, and allow to stand until the phases separate. Transfer the organic phase to a suitable glass vial. Repeat the extraction with a second 2-mL portion of isopropyl alcohol, and transfer the organic phase to the same vial. Evaporate the solution under a stream of nitrogen. Dry the residue in an oven at 100° for 30 min, allow to cool to room temperature in a desiccator, and prepare a mull by the addition of 1–2 drops of Mineral oil.

Acceptance criteria: Meets the requirements Add the following:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 1S (USP41)

3 ASSAY

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PROCEDURE

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 hy droxide to a pH of 6.5, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (25:75)

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

System suitability solution: 0.14 mg/mL of USP Sumatriptan Succinate RS and 0.07 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: Nominally equivalent to 0.1 mg/mL of sumatriptan in Diluent from an appropriate volume of Nasal Spray Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 282 nm

Column: 4.6-mm × 20-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 4 times the retention of sumatriptan 1S (USP41)

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 the labeled amount of sumatriptan (C₁₄H₂₁N₃O₂S) in the portion of Nasal Spray 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 (ERR 1-Oct-2018) in the Standard solution (mg/mL)

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

M_r1 = molecular weight of sumatriptan, 295.401S (USP41)

M_r2 = molecular weight of sumatriptan succinate, 413.491S (USP41)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

DELIVERABLE VOLUME

Analysis: Test 10 vials separately. Weigh each vial before and after actuation, and calculate the individual volume delivered, in µL, then calculate the mean volume delivered:

Result = (W₁ − W₂)/D

W₁ = weight of the individual vial before actuation (mg)

W₂ = weight of the individual vial after actuation (mg)

D = density of the nasal solution

Acceptance criteria: The volume of each spray delivered is between 80 and 120 µL, and the mean volume is between 90 and 110 µL.

5 IMPURITIES

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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)

Diluent: Prepare as directed in the Assay.

Standard solution: 0.007 mg/mL1S (USP41) of USP Sumatriptan Succinate Related Compound A RS in Diluent

Sample solution: Nominally equivalent to 1.0 mg/mL of sumatriptan in Diluent from an appropriate volume of Nasal Spray Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 282 nm

Column: 4.6-mm × 20-cm; packing L3

Flow rate: 2 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention of sumatriptan related compound A 1S (USP41)

System suitability

Sample: Standard solution Suitability requirements

Relative standard deviation: NMT 5% Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sumatriptan succinate related compound A in the portion of Nasal Spray taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of sumatriptan related compound A from the Sample solution

r_S = peak response of sumatriptan related compound A from the Standard solution

C_S = concentration of USP Sumatriptan Succinate Related Compound A RS1S (USP41) in the Standard solution (mg/mL)

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

M_r1 = molecular weight of sumatriptan related compound A, 495.681S (USP41)

M_r2 = molecular weight of sumatriptan succinate related compound A, 613.771S (USP41)

Acceptance criteria: NMT 1.5%

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ORGANIC IMPURITIES

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

Mobile phase: Acetonitrile and Buffer (25:75) Diluent: Prepare as directed in the Assay.

System suitability solution: 1.4 mg/mL of USP Sumatriptan Succinate RS and 1 µg/mL of USP Sumatriptan Succinate Related Compound C RS in Diluent

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

Sample solution: Nominally equivalent to 1 mg/mL of sumatriptan in Diluent from an appropriate volume of Nasal Spray Chromatographic system: Proceed as directed in the Assay. 1S (USP41)

System suitability

Sample: System suitability solution

[NOTE—See Table 1 for the relative retention times.]    1S (USP41)

Suitability requirements

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

Samples: Identification solution and1S (USP41) Sample solution

Calculate the percentage of each degradation product1S (USP41) in the portion of Nasal Spray taken:

Result = (r_U/r_T) × (1/F) × 100           1S (USP41)

r_U = peak response of each degradation product1S (USP41) from the Sample solution

r_T = sum of all the peak responses from the Sample solution

F = relative response factor