Rizatriptan Benzoate Orally Disintegrating 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 Orally Disintegrating 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

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

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

3 ASSAY

Procedure

Buffer:

Transfer 3.4 g monobasic potassium phosphate + 2.0 g sodium 1-heptanesulfonate → 1-L volumetric flask + 900 mL water.

Adjust pH to 7.5 with 50% NaOH (w/w). Dilute to volume.

Mobile phase: Acetonitrile : Buffer (16:84)

Diluent: Acetonitrile : 0.025 M monobasic potassium phosphate (10:90)

Standard solution:

0.07 mg/mL USP Rizatriptan Benzoate RS in Diluent

Sample stock solution:

Nominal 0.5 mg/mL rizatriptan in Diluent:

Transfer NLT 10 Tablets, add 25–50% flask volume of Diluent, swirl to disintegrate, dilute to volume.

Sample solution:

Nominal 0.05 mg/mL rizatriptan free base from Sample stock in Diluent.

Chromatographic system

Mode: LC

Detector: UV 226 nm

(For Identification B: diode array 210–400 nm)

Column: 4.6 mm × 25 cm; 5 µm L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 1.5 × rizatriptan retention time

System suitability

Sample: Standard solution

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

Requirements:

Tailing factor ≤ 3.5

RSD ≤ 2.0% for rizatriptan peak

Analysis

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

rᵤ = peak response, Sample

rₛ = peak response, Standard

Cₛ = concentration of Standard (mg/mL)

Cᵤ = nominal concentration 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〉

Test 1

Medium: Water, 900 mL

Apparatus 2: 50 rpm

Time: 5 min

Standard solution:

(L/625) mg/mL USP Rizatriptan Benzoate RS,

where L = label claim (mg/Tablet)

Sample solution:

Filter through 10-µm membrane.

Instrumental conditions:

Mode: UV

Wavelengths: 278 nm and 320 nm

Analysis

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

Aᵤ = absorbance (Sample), corrected at 320 nm

Aₛ = absorbance (Standard), corrected at 320 nm

C = concentration of Standard (mg/mL)

V = volume = 900 mL

Mᵤ = 269.35

Mₛ = 391.47

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) dissolved.

Test 2

(If tested, labeling must state Dissolution Test 2.)

Medium: deaerated water, 900 mL

Apparatus 2: 50 rpm

Time: 10 min

Buffer: 2.7 g monobasic potassium phosphate in 1 L water + 2 mL triethylamine → adjust pH 5.0 with phosphoric acid (1:10).

Mobile phase: Methanol : Buffer (10:90)

Standard solution:

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

Sample solution:

Filter through 0.45-µm membrane

Chromatographic system

Mode: LC

Detector: UV 225 nm

Column: 4.6 mm × 15 cm; 5 µm L7

Temperature: 40°

Flow: 1.5 mL/min

Injection: 20 µL

Run time: NLT 2 × rizatriptan retention time

System suitability

Sample: Standard solution

Tailing factor ≤ 2.0

RSD ≤ 2.0%

Analysis

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

rᵤ = peak response (Sample)

rₛ = peak response (Standard)

C = concentration of Standard

Mᵤ = 269.35

Mₛ = 391.47

V = 900 mL

L = label claim

Tolerance: NLT 80% (Q) dissolved.

Uniformity of Dosage Units 〈905〉

Meets the requirements.

5 IMPURITIES

Organic Impurities

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

System suitability stock A: Rizatriptan N-oxide preparation

Detailed preparation (heating, peroxide, etc.) — retained fully.

System suitability stock B: N-methyl adduct preparation

(Heated with dimethylcarbonate → reflux → pH adjustment).

System suitability solution: Stock A + Stock B + Standard (4:4:2)

Sensitivity solution:

0.07 µg/mL Rizatriptan Benzoate RS

System suitability

Samples:

Standard solution

System suitability solution

Sensitivity solution

Requirements:

Resolution ≥ 2 (N-methyl adduct vs rizatriptan)

Tailing ≤ 3.5

S/N ≥ 10

Analysis

Result = (rᵢ / rₜₒₜₐₗ) × 100

rᵢ = response of individual degradation product

rₜₒₜₐₗ = sum of areas of rizatriptan + all degradation products

(excluding benzoic acid + process impurities)

Reporting threshold: 0.1%

ᵃ Counterion (not reported nor included in totals)

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

ᶜ Excipient; may not appear in all formulations

ᵈ 2-{5-[(1H-1,2,4-Triazol-1-yl)methyl]-1H-indol-3-yl}-N-methylethanamine

ᵉ 2-{5-[(1H-1,2,4-Triazol-1-yl)methyl]-1H-indol-3-yl}-N,N,N-trimethylethan-1-aminium

ᶠ Process impurities controlled in drug substance (excluded from totals)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage:

Preserve in well-closed, light-resistant containers.

Store at controlled room temperature.

Labeling:

If Test 1 is not used, label must specify the dissolution test applied.

USP Reference Standards 〈11〉

USP Rizatriptan Benzoate RS