Rizatriptan Benzoate 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

Rizatriptan Benzoate Tablets contain an amount of rizatriptan benzoate (C₁₅H₁₉N₅ · C₇H₆O₂) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of rizatriptan (C₁₅H₁₉N₅).

2 IDENTIFICATION

Change to read:

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

Sample: Grind a suitable number of Tablets containing NLT 125 mg of rizatriptan. Transfer a suitable amount of powder equivalent to NLT 100 mg of rizatriptan to a suitable flask to obtain a 5 mg/mL solution. Add 75% of the flask volume of methanol. Shake vigorously to disperse the powder. Dilute with methanol to volume. Pass a portion through a suitable filter. Evaporate the filtrate under a stream of nitrogen. Prepare a mull of the residue with Mineral oil.

Acceptance criteria: The spectrum of the Sample corresponds to that of a similarly prepared Standard.

B. The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer:

Dissolve 1.7 g of monobasic potassium phosphate and 0.9 g of sodium 1-hexanesulfonate to a 1-L volumetric flask. Add 900 mL of water. Adjust with 50% (w/w) sodium hydroxide solution to a pH of 6.8. Dilute with water to volume.

Mobile phase: Acetonitrile and Buffer (15:85)

Diluent: Acetonitrile and 0.05 M ammonium acetate (20:80)

Standard solution: 0.06 mg/mL of USP Rizatriptan Benzoate RS in Diluent

Sample stock solution:

Nominally 0.2 mg/mL of rizatriptan in Diluent prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask. Add 10%–20% of the flask volume of Diluent. Swirl until the Tablets have disintegrated completely. Dilute with Diluent to volume. Stir the solution for 90–150 min. Centrifuge a portion of the resulting solution. Use the supernatant to prepare the Sample solution.

Sample solution:

Nominally 0.04 mg/mL of rizatriptan from the supernatant of the Sample stock solution and Diluent.

Chromatographic system

Mode: LC

Detector: UV 226 nm

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

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2.5 × retention time of rizatriptan

[Note—A suitable guard column may be used if necessary.]

System suitability

Sample: Standard solution

[Note—See Table 1 for relative retention times.]

Requirements:

Tailing factor: NMT 3

RSD: NMT 2.0% for the rizatriptan peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of rizatriptan (C₁₅H₁₉N₅):

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (Mᵤ / Mₛ) × 100

rᵤ = peak response of rizatriptan from the Sample solution

rₛ = peak response of rizatriptan from the Standard solution

Cₛ = concentration of USP Rizatriptan Benzoate RS in the Standard (mg/mL)

Cᵤ = nominal concentration of rizatriptan in Sample (mg/mL)

Mᵤ = MW of rizatriptan = 269.35

Mₛ = MW of rizatriptan benzoate = 391.47

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Instrumental procedure

Medium: Water, deaerated if necessary; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Standard solution:

(L/625) mg/mL of USP Rizatriptan Benzoate RS in Medium

L = label claim (mg/Tablet)

Sample solution:

Filter through 10-µm membrane.

Instrumental conditions

Mode: UV

Wavelength: 226 nm

Analysis

Samples: Standard + Sample

Result = (Aᵤ / Aₛ) × C × V × (Mᵤ / Mₛ) × (1/L) × 100

Aᵤ = absorbance of Sample

Aₛ = absorbance of Standard

C = concentration of Standard (mg/mL)

V = volume = 900 mL

Mᵤ = 269.35

Mₛ = 391.47

L = label claim

Chromatographic procedure

Buffer: 1.36 g/L monobasic potassium phosphate → adjust pH to 2.5 with phosphoric acid

Mobile phase: Acetonitrile : Buffer (10:90)

Standard stock solution: 0.4 mg/mL USP Rizatriptan Benzoate RS in Medium

Standard solution: (L/900) mg/mL rizatriptan from stock + Medium

Sample solution: Filter through 10-µm membrane

Chromatographic system

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 15-cm; 3.5-µm L10

Column temp: 40°

Flow: 1 mL/min

Injection: 10 µL

Run time: NLT 2 × retention time

System suitability

Sample: Standard solution

Requirements:

Tailing ≤ 2.0

RSD ≤ 2.0%

Analysis

Result = (rᵤ / rₛ) × C × V × (Mᵤ / Mₛ) × (1/L) × 100

rᵤ = peak response, Sample

rₛ = peak response, Standard

C = concentration of Standard

V = 900 mL

Mᵤ = 269.35

Mₛ = 391.47

L = label claim

Tolerance: NLT 80% (Q) dissolved.

Uniformity of Dosage Units 〈905〉

Meets requirements.

5 IMPURITIES

Organic Impurities

Mobile phase, Diluent, Standard solution, Sample solution, chromatographic system: per Assay.

System suitability solution:

Rizatriptan + benzoic acid + rizatriptan N-oxide prepared by peroxide oxidation

(stated heating + timing procedure retained fully).

[Solution stable ≥7 days at RT.]

Sensitivity solution: 0.06 µg/mL USP Rizatriptan Benzoate RS from Standard solution + water

System suitability

Samples:

Standard

System suitability solution

Sensitivity solution

Requirements:

Resolution: NLT 2.0 (benzoic acid vs N-oxide)

Tailing: NMT 3 (rizatriptan peak)

S/N: NLT 10 (Sensitivity solution)

Analysis

Sample: Sample solution

Result = (rᵢ / rₜₒₜₐₗ) × 100

rᵢ = peak response of each degradation product

rₜₒₜₐₗ = sum of peak responses of rizatriptan + all degradation products (except benzoic acid + process impurities)

Acceptance criteria: See Table 1

Ignore impurities <0.1%.

ᵃ Not an impurity; counterion

ᵇ 2-{5-[(1H-1,2,4-Triazol-1-yl)methyl]-1H-indol-3-yl}-N,N-dimethylethanamine oxide

ᶜ Exclude benzoic acid and process impurities

6 ADDITIONAL REQUIREMENTS

Packaging and Storage:

Preserve in well-closed, light-resistant containers.

Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Rizatriptan Benzoate RS