Zolmitriptan 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

Zolmitriptan Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of zolmitriptan (C₁₆H₂₁N₃O₂).

2 IDENTIFICATION

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

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: Dissolve 2 mL of triethylamine in 1 L of water. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (15:85)

Standard stock solution: 0.25 mg/mL of USP Zolmitriptan RS in methanol

Standard solution: 0.025 mg/mL of USP Zolmitriptan RS in Mobile phase from a suitable volume of Standard stock solution

Sample stock solution: 0.25 mg/mL of zolmitriptan in methanol, prepared as follows. Transfer NLT 20 Tablets to a suitable volumetric flask.

Add 75% of the flask volume of methanol. Sonicate for 30 min. Allow to cool to room temperature and dilute with methanol to volume.

Sample solution: Nominally 0.025 mg/mL of zolmitriptan in Mobile phase from a suitable volume of Sample stock solution. Pass a portion of the solution under test through a suitable membrane filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm. For Identification test A, use a diode-array detector in the wavelength range of 200–300 nm.

Column: 4.6-mm × 15-cm; 5-μm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 2.5 times the retention time of zolmitriptan

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolmitriptan (C₁₆H₂₁N₃O₂) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of zolmitriptan from the Sample solution

r_S = peak response of zolmitriptan from the Standard solution

C_S = concentration of USP Zolmitriptan RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Disintegration 〈701〉: NMT 30 s

Change to read:

Dissolution 〈711〉

Test 1 (RB 1-May-2020)

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 50 rpm

Time: 15 min

Analyze the sample under test using either the Chromatographic procedure or the Spectroscopic procedure. (RB 1-May-2020)

Chromatographic procedure

Buffer, Mobile phase, Standard stock solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard solution: 0.005 mg/mL of USP Zolmitriptan RS from Standard stock solution in Medium

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolmitriptan (C₁₆H₂₁N₃O₂) dissolved:

Result = (r_U /r_S) × C_S × V × (1/L) × 100

r_U = peak response of zolmitriptan from the Sample solution

r_S = peak response of zolmitriptan from the Standard solution

C_S = concentration of USP Zolmitriptan RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim of zolmitriptan (mg/Tablet) Spectroscopic procedure (RB 1-May-2020)

Standard solution: 0.01 mg/mL of USP Zolmitriptan RS from Standard stock solution in Medium

Sample solution: Pass a portion of the solution under test through a suitable membrane filter of 0.2-μm pore size.

Instrumental conditions

Mode: UV

Analytical wavelength: About 283 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolmitriptan (C₁₆H₂₁N₃O₂) dissolved:

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Zolmitriptan RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim of zolmitriptan (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of zolmitriptan (C₁₆H₂₁N₃O₂) is dissolved.

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

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 50 rpm

Time: 15 min

Buffer: Add 7.8 g of monobasic sodium phosphate to 1000 mL of water. Adjust with phosphoric acid to a pH of 2.5.

Mobile phase: Acetonitrile and Buffer (15:85)

Standard stock solution: 0.33 mg/mL of USP Zolmitriptan RS prepared as follows. Transfer a suitable quantity of USP Zolmitriptan RS to an appropriate volumetric flask and add 70% of the flask volume of Medium. Sonicate to aid dissolution. Dilute with Medium to volume.

Standard solution: (L/500) mg/mL of zolmitriptan from Standard stock solution in Medium, where L is the label claim of zolmitriptan in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 15-cm; 3-μm packing L1

Temperatures:

Autosampler: 5°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 2 times the retention time of zolmitriptan

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolmitriptan (C₁₆H₂₁N₃O₂) dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × 100

r_U = peak response of zolmitriptan from the Sample solution

r_S = peak response of zolmitriptan from the Standard solution

C_S = concentration of USP Zolmitriptan RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim of zolmitriptan (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of zolmitriptan (C₁₆H₂₁N₃O₂) is dissolved. (RB 1-May-2020)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Diluent: Methanol and water (25:75)

Solution A: 2.7 g/L of monobasic potassium phosphate in water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Impurities stock solution: 0.2 mg/mL each of USP Zolmitriptan Related Compound E RS and USP Zolmitriptan Related Compound G RS in methanol

System suitability solution: 0.25 mg/mL of USP Zolmitriptan RS and 0.002 mg/mL each of USP Zolmitriptan Related Compound E RS and USP Zolmitriptan Related Compound G RS in Diluent prepared as follows. Dissolve a suitable quantity of USP Zolmitriptan RS in a suitable volumetric flask containing 50% of the flask volume of Diluent. Sonicate to dissolve. Transfer a suitable volume of Impurities stock solution to the flask. Dilute with Diluent to volume.

Standard stock solution: 0.25 mg/mL of USP Zolmitriptan RS in methanol

Standard solution: 0.001 mg/mL of USP Zolmitriptan RS from Standard stock solution in Diluent

Sample solution: Nominally 0.25 mg/mL of zolmitriptan from NLT 5 Tablets prepared as follows. Transfer the required number of Tablets to a suitable volumetric flask. Add 25% of the flask volume of methanol. Sonicate for 30 min with intermittent shaking. Cool to room temperature. Dilute with water to volume. Pass through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector

For zolmitriptan and zolmitriptan related compound E and any other unspecified degradation products: UV 223 nm

For zolmitriptan and zolmitriptan related compound G: UV 235 nm

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

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[Note - See Table 2 for relative retention times.]

Suitability requirements: Use 223 nm for system suitability evaluation.

Resolution: NLT 5.0 between zolmitriptan and zolmitriptan related compound E, System suitability solution

Tailing factor: NMT 2.0 for zolmitriptan, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of zolmitriptan related compound G in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of zolmitriptan related compound G at 235 nm from the Sample solution

r_S = peak response of zolmitriptan at 235 nm from the Standard solution

C_S = concentration of USP Zolmitriptan RS in the Standard solution (mg/mL)

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

F = relative response factor for zolmitriptan related compound G (see Table 2)

Calculate the percentage of zolmitriptan related compound E and any other unspecified degradation product in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of zolmitriptan related compound E or any other unspecified degradation product at 223 nm from the Sample solution

r_S = peak response of zolmitriptan at 223 nm from the Standard solution

C_S = concentration of USP Zolmitriptan RS in the Standard solution (mg/mL)

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any impurity less than 0.05%.

Table 2

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers. Store at controlled room temperature.

Add the following:

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. (RB 1-May-2020)

USP Reference Standards 〈11〉

USP Zolmitriptan RS

USP Zolmitriptan Related Compound E RS

(S)-N,N-Dimethyl-2-{5-[(2-oxooxazolidin-4-yl)methyl]-1H-indol-3-yl}ethanamine oxide.

C₁₆H₂₁N₃O₃ 303.36

USP Zolmitriptan Related Compound G RS

(S)-4-(4-Aminobenzyl)oxazolidin-2-one.

C₁₀H₁₂N₂O₂ 192.21