Alosetron Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Alosetron Tablets contains an amount of Alosetron Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of alosetron (C₁₇H₁₈N₄O).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 197U (CN 1-MAY-2020) [NOTE-The UV spectra of the major peaks of the Sample solution and the Standard solution as obtained in the Assay may also be used to meet the Acceptance criteria.]

Standard stock solution: 0.115 mg/mL of USP Alosetron Hydrochloride RS in water

Standard solution: 2.3 µg/mL of USP Alosetron Hydrochloride RS in water, from the Standard stock solution

Sample solution: Transfer a number of Tablets, nominally equivalent to 1 mg of alosetron, to a 250-mL volumetric flask. Fill the flask to about 3/4 full with water and shake for 30 min. Dilute with water to volume, mix, and pass through a PVDF filter or other suitable filter of 0.45-µm pore size, discarding at least 15 mL of the filtrate.

Wavelength range: 200-400 nm

Cell: 1 cm

Blank: Water

Acceptance criteria: The spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution, concomitantly measured.

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 solutions containing alosetron hydrochloride from light.

Buffer: 0.02 M monobasic sodium phosphate. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Buffer and acetonitrile (80:20)

Diluent: Mix 1 mL of phosphoric acid with 1000 mL of water.

Standard stock solution: 0.115 mg/mL of USP Alosetron Hydrochloride RS in Diluent

Standard solution: 0.0115 mg/mL of USP Alosetron Hydrochloride RS in Diluent, from the Standard stock solution

Sample solution: Nominally 0.01 mg/mL of alosetron prepared as follows. Transfer 10 Tablets to a suitable volumetric flask. Fill the flask to about 3/4 full with Diluent, shake for 10 min, and then sonicate for another 10 min. Dilute with Diluent to volume, mix, let the solids settle, and pass through a PVDF filter or other suitable filter of 0.45-µm pore size, discarding at least 6 mL of the filtrate.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 7.5-cm; 3-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 15 µL

Autosampler temperature: 5°

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of alosetron (C₁₇H₁₈N₄O) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

M_r1 = molecular weight of alosetron, 294.36

M_r2 = molecular weight of alosetron hydrochloride, 330.82

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Protect solutions containing alosetron hydrochloride from light.

Medium: Water (deaerated): 500 mL

Apparatus 2: 75 rpm

Time: 20 min

Mobile phase: Prepare as directed in the Assay.

Sample solution: Pass a portion of the solution under test through a PVDF filter or other suitable filter of 0.45-µm pore size, discarding at least 15 mL of the filtrate.

Standard stock solution: 0.115 mg/mL of USP Alosetron Hydrochloride RS in Medium

Standard solution: 2.3 µg/mL of USP Alosetron Hydrochloride RS in water, from the Standard stock solution. Further dilute with Medium, if needed, to a concentration that is similar to that of the Sample solution.

Chromatographic system: Proceed as directed in the Assay, except for Injection volume.

Injection volume: 75 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 3.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of the labeled amount of alosetron (C₁₇H₁₈N₄O) dissolved:

Result = (r_U/r_S) x (C_S/L) x (M_r1/M_r2) x 100

r_U = peak response of alosetron from the Sample solution

r_S = peak response of alosetron from the Standard solution

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

L = labeled amount of alosetron (mg/Tablet)

V = volume of Medium, 500 mL

M_r1 = molecular weight of alosetron, 294.36

M_r2 = molecular weight of alosetron hydrochloride, 330.82

Tolerances: NLT 80% (Q) of the labeled amount of alosetron (C₁₇H₁₈N₄O) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Protect solutions containing alosetron hydrochloride from light.

Buffer: Prepare as directed in the Assay.

Solution A: Buffer

Solution B: Acetonitrile

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system for at least 10 min.

Table 1

Diluent: Buffer and acetonitrile (90:10)

System suitability solution: 200 µg/mL of USP Alosetron Hydrochloride RS and 0.5 µg/mL of USP Alosetron Related Compound A RS in Diluent

Standard stock solution: 0.115 mg/mL of USP Alosetron Hydrochloride RS in Diluent

Standard solution: 0.46 µg/mL of USP Alosetron Hydrochloride RS in Diluent, from the Standard stock solution

Sample solution: Nominally 200 µg/mL of alosetron prepared as follows. Transfer a number of Tablets, equivalent to 5 mg of alosetron, to a suitable container. Add 25 mL of Diluent, shake for 10 min, and then sonicate for another 20 min. Mix, let the solids settle, and pass through a PVDF filter or other suitable filter of 0.45-um pore size, discarding at least 6 mL of the filtrate.

Chromatographic system: Proceed as directed in the Assay, except for Injection volume.

Injection volume: 5 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 7 between alosetron and alosetron related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x (M_r1/M_r2) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of alosetron from the Standard solution

C_S = concentration of USP Alosetron Hydrochloride RS in the Standard solution (µg/mL)

C_U = nominal concentration of alosetron in the Sample solution (µg/mL)

F = relative response factor (see Table 2)

M_r1 = molecular weight of alosetron, 294.36

M_r2 = molecular weight of alosetron hydrochloride, 330.82

Acceptance criteria: See Table 2.

Table 2

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature, protected from light.

USP REFERENCE STANDARDS (11).

USP Alosetron Hydrochloride RS

USP Alosetron Related Compound A RS

Dealkyl alosetron;

5-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one.

C₁₂H₁₂N₂O 200.24(USP 1-Dec-2019)