Almotriptan 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

Almotriptan Tablets contain an amount of almotriptan malate (C₁₇H₂₅N₃O₂S · C₄H₆O₅) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of almotriptan (C₁₇H₂₅N₃O₂S).

2 IDENTIFICATION

2.1 Change to read

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

Sample: Sonicate 5 powdered Tablets in 25 mL of water. Extract the suspension with 25 mL of methylene chloride, and discard the organic phase. Add another 25 mL of methylene chloride and 3 mL of 1 N sodium hydroxide. Extract the precipitated base into the organic layer. Dry with anhydrous sodium sulfate, and evaporate the organic solvent. Prepare the residue oil as a film on a sodium chloride pellet.

Acceptance criteria: The IR spectrum obtained from the Sample is consistent with that of similarly prepared USP Almotriptan Malate RS.

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

3.1 Procedure

Protect samples, the Reference Standards, and solutions containing them from light.

Buffer: Add 10 mL of triethylamine to every 1000 mL of 0.01 M phosphoric acid. Adjust with phosphoric acid to a pH of 6.0.

Mobile phase: Acetonitrile and Buffer (10:90)

Standard solution: 0.5 mg/mL of USP Almotriptan Malate RS in Mobile phase. Sonication may be used to aid in dissolution.

System suitability stock solution: 0.1 mg/mL each of USP Almotriptan Related Compound B RS, USP Almotriptan Related Compound C RS, and USP Almotriptan Related Compound D RS in methanol. Sonication may be used to aid in dissolution.

System suitability solution: 0.001 mg/mL each of USP Almotriptan Related Compound B RS, USP Almotriptan Related Compound C RS, and USP Almotriptan Related Compound D RS prepared from the System suitability stock solution in Standard solution

Sample solution: Nominally 0.5 mg/mL of almotriptan from Tablets prepared as follows. Transfer NLT 8 Tablets into a suitable volumetric flask, and add 80% of the flask volume of Mobile phase. Sonicate for NLT 10 min, and dilute with Mobile phase to volume. Stir for 30 min, and centrifuge. Pass a portion of the supernatant through a suitable filter of 0.45-μm pore size. Use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 2.1-mm × 10-cm; 1.8-μm packing L1

Column temperature: 40°

Flow rate: 0.55 mL/min

Injection volume: 3 μL

System suitability

Samples: Standard solution and System suitability solution

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

Suitability requirements

Resolution: NLT 1.5 between almotriptan related compound C and almotriptan peaks, System suitability solution

Tailing factor: NMT 3.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of almotriptan (C₁₇H₂₅N₃O₂S) in the portion of Tablets taken:

Result = (r_u /r_s) × (C_s/C_u) × (M_r1/M_r2) × 100

r_u = peak response of almotriptan from the Sample solution

r_s = peak response of almotriptan from the Standard solution

C_s = concentration of USP Almotriptan Malate RS in the Standard solution (mg/mL)

C_u = nominal concentration of almotriptan in the Sample solution (mg/mL)

M_r1= molecular weight of almotriptan, 335.46

M_r2= molecular weight of almotriptan malate, 469.55

Acceptance criteria: 90.0%–110.0% of the labeled amount of almotriptan

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Standard solution: (L/600) mg/mL of USP Almotriptan Malate RS in Medium, where L is the label claim in mg/Tablet

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

Instrumental conditions

Mode: UV

Analytical wavelength

For Tablets labeled to contain 6.25 mg: 228 nm

For Tablets labeled to contain 12.5 mg: 284 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of almotriptan (C₁₇H₂₅N₃O₂S) dissolved:

Result = (A_u /A_s) × (C_s/L) × V × (M_r1/M_r2) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Almotriptan Malate RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

M_r1 = molecular weight of almotriptan, 335.46

M_r2 = molecular weight of almotriptan malate, 469.55

Tolerances: NLT 80% (Q) of the labeled amount of almotriptan (C₁₇H₂₅N₃O₂S) 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; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard stock solution: 0.425 mg/mL of USP Almotriptan Malate RS, equivalent to 0.30 mg/mL of almotriptan, in water

Standard solution: 0.021 mg/mL of USP Almotriptan Malate RS, equivalent to 0.015 mg/mL of almotriptan, from the Standard stock solution in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, and discard the first 5 mL. Use the remaining filtrate.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 283 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of almotriptan (C₁₇H₂₅N₃O₂S) dissolved:

Result = (A_u /A_s) × (C_s/L) × V × (M_r1/M_r2) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Almotriptan Malate RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

M_r1 = molecular weight of almotriptan, 335.46

M_r2 = molecular weight of almotriptan malate, 469.55

Tolerances: NLT 80% (Q) of the labeled amount of almotriptan (C₁₇H₂₅N₃O₂S) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

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

Analysis

Samples: Standard solution, System suitability solution, and Sample solution

Chromatograph the System suitability solution and identify the components on the basis of their relative retention times, as shown in

Table 1.

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (r_u /r_s) × (C_s/C_u) × (M_r1/M_r2) × 100

r_u = peak response of each degradation product from the Sample solution

r_s = peak response of almotriptan from the Standard solution

C_s = concentration of USP Almotriptan Malate RS in the Standard solution (mg/mL)

C_u = nominal concentration of almotriptan in the Sample solution (mg/mL)

M_r1 = molecular weight of almotriptan, 335.46

M_r2 = molecular weight of almotriptan malate, 469.55

Acceptance criteria: See Table 1.

a 1′-Methyl-5-[(pyrrolidin-1-ylsulfonyl)methyl]spiro[indoline-3,3′-pyrrolidin]-2-ol.

b 3-[2-(Dimethylamino)ethyl]-5-[(pyrrolidin-1-ylsulfonyl)methyl]-1H-indol-2-ol.

c This is a process impurity that is included in this table for identification only. This impurity is controlled in the drug substance. This impurity is not to be reported for the drug product and is not to be included in the total degradation products.

6 ADDITIONAL REQUIREMENTS

6.1 Packaging and Storage:

Preserve in tight, light-resistant containers. Store at controlled room temperature.

6.2 Labeling:

The labeling states the Dissolution test used only if Test 1 is not used.

6.3 USP Reference Standards 〈11〉

USP Almotriptan Malate RS

USP Almotriptan Related Compound B RS

2-{5-[(Pyrrolidin-1-ylsulfonyl)methyl]-1H-indol-3-yl}ethanamine hemifumarate.

C₁₅H₂₁N₃O₂S .1⁄2  C₄H₄O₄ 365.46

USP Almotriptan Related Compound C RS

N-Methyl-2-{5-[(pyrrolidin-1-ylsulfonyl)methyl]-1H-indol-3-yl}ethanamine.

C₁₆H₂₃N₃O₂S 321.44

USP Almotriptan Related Compound D RS

1-[({3-[2-(Dimethylamino)ethyl]indol-5-yl}methyl)sulfonyl]pyrrolidine N-oxide hydrochloride.

C₁₇H₂₅N₃O₃S · HCl 387.92