Rizatriptan Benzoate

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 contains NLT 98.0% and NMT 102.0% of C₂₂H₂₅N₅O₂, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

[Note—If the spectra obtained show differences, dissolve the substance to be examined and the Reference Standard separately in methanol, evaporate to dryness, and record the new spectra using the residues.]

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

[Note—Use silanized autosampler vials and freshly prepared solutions.]

Solution A: Add 1.0 mL of trifluoroacetic acid to 1 L of a solution of acetonitrile and water (4:21), and mix.

Solution B: Acetonitrile and trifluoroacetic acid (1000:1)

Standard solution: 1 mg/mL of USP Rizatriptan Benzoate RS in Solution A

Sample solution: 1 mg/mL of Rizatriptan Benzoate in Solution A

Mobile phase: See gradient table below.

Gradient Table

Chromatographic system

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 25-cm; 5-µm packing L11

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection size: 20 µL

[Note—The relative retention times for rizatriptan and benzoic acid are 1.0 and about 2.1.]

System suitability

Sample: Standard solution

Requirements:

Tailing factor: NMT 3.5 for rizatriptan

RSD: NMT 0.73% for the rizatriptan peak

Analysis

Samples: Standard + Sample solution

Calculate % of C₂₂H₂₅N₅O₂:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of rizatriptan from Sample

rₛ = peak response of rizatriptan from Standard

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

Cᵤ = concentration of Rizatriptan Benzoate in Sample (mg/mL)

Acceptance criteria: 98.0%–102.0% (anhydrous)

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Procedure

Solution A, Solution B, Mobile phase: As in Assay

Sample solution: 1 mg/mL Rizatriptan Benzoate in Solution A

System suitability solution: 1 mg/mL USP Rizatriptan Benzoate System Suitability Mixture RS in Solution A

Sensitivity solution: 0.5 µg/mL Rizatriptan Benzoate (by dilution of Sample with Solution A)

Chromatographic system: Same as Assay

System suitability

Samples: System suitability + Sensitivity solution

[Note—RRTs for rizatriptan, rizatriptan impurity C, benzoic acid ≈ 1.0, 1.3, 2.1]

Requirements:

Resolution: NLT 2.0 (rizatriptan vs impurity C)

S/N: NLT 10 (rizatriptan peak, Sensitivity)

Analysis

Sample: Sample solution

Result = [rᵤ / (r_t − r_ba)] × 100

rᵤ = peak response of each impurity

r_t = sum of all peaks in Sample

r_ba= benzoic acid peak area

Acceptance criteria:

Any individual impurity: NMT 0.10%

Total impurities: NMT 0.3%

[Disregard impurities < 0.05%.]

5 SPECIFIC TESTS

Water Determination, Method Ia 〈921〉: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage:

Store in well-closed containers at room temperature.

USP Reference Standards 〈11〉

USP Rizatriptan Benzoate RS

USP Rizatriptan Benzoate System Suitability Mixture RS

Mixture contains rizatriptan benzoate + ≥0.1% of rizatriptan impurity C.

Rizatriptan impurity C =

2-{5-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indol-2-yl}-N,N-dimethylethanamine (C₁₅H₁₉N₃ 269.35)