Printed on: Wed Feb 08 2023, 11:15:07 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-46606CBE-8631-48D4-BA9A-612EDC69694F_5_en-US

Printed by: Dang Van Vu Official Date: Official as of 01-May-2020 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: md1t3 DOI: https://doi.org/10.31003/USPNF_M1550_05_01
1

Acceptance criteria: 98.0%–102.0% on the anhydrous

Alosetron Hydrochloride basis
IMPURITIES
• RESIDUE ON IGNITION á281ñ: NMT 0.2%

Change to read:
C17H18N4O · HCl 330.82 • ORGANIC IMPURITIES
1H-Pyrido[4,3-b]indol-1-one, 2,3,4,5-tetrahydro-5-methyl-2- Protect solutions containing alosetron hydrochloride from
[(5-methyl-1H-imidazol-4-yl)methyl]-, hydrochloride; light.
2,3,4,5-Tetrahydro-5-methyl-2-[(5-methylimidazol-4-yl) Buffer and Chromatographic system: Proceed as directed
methyl]-1H-pyrido[4,3-b]indol-1-one hydrochloride in the Assay.
CAS RN®: 122852-69-1. Solution A: Buffer
Solution B: Acetonitrile
DEFINITION Mobile phase: See Table 1. Return to original conditions
Alosetron Hydrochloride contains NLT 98.0% and NMT and re-equilibrate the system.
102.0% of alosetron hydrochloride (C17H18N4O · HCl),
calculated on the anhydrous basis. Table 1
IDENTIFICATION Time Solution A Solution B
(min) (%) (%)
Change to read: 0 90 10

al
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared 5 90 10
Spectroscopy: 197A OR 197K▲ (CN 1-May-2020) Meets the
20 50 50
requirements
• B. The retention time of the major peak of the Sample 25 50 50
solution corresponds to that of the Standard solution, as ci
obtained in the Assay. Diluent: Buffer and acetonitrile (90:10)
• C. IDENTIFICATION TESTS—GENERAL á191ñ, Chloride: Meets System suitability solution: 0.5 mg/mL of USP Alosetron
the requirements of the silver nitrate precipitation test Hydrochloride RS and 0.5 µg/mL of USP Alosetron Related
ASSAY Compound A RS in Diluent
• PROCEDURE Standard solution: 0.5 µg/mL of USP Alosetron
ffi
Protect solutions containing alosetron hydrochloride from Hydrochloride RS in Diluent
light. Sensitivity solution: 0.25 µg/mL of USP Alosetron
Buffer: 0.02 M monobasic sodium phosphate. Adjust with Hydrochloride RS in Diluent from the Standard solution
phosphoric acid to a pH of 3.0. Sample solution: 500 µg/mL of Alosetron Hydrochloride in
Mobile phase: Buffer and acetonitrile (80:20) Diluent
Standard solution: 0.05 mg/mL of USP Alosetron System suitability
O

Hydrochloride RS in Mobile phase Samples: System suitability solution, Standard solution, and
Sample solution: 0.05 mg/mL of Alosetron Hydrochloride Sensitivity solution
in Mobile phase Suitability requirements
Chromatographic system Resolution: NLT ▲3▲ (ERR 1-May-2020) between alosetron and
(See Chromatography á621ñ, System Suitability.) alosetron related compound A, System suitability solution
Mode: LC Relative standard deviation: NMT 5.0%, Standard
Detector: UV 220 nm solution
Column: 4.6-mm × 7.5-cm; 3-µm packing L1 Signal-to-noise ratio: NLT 10, Sensitivity solution
Flow rate: 1.0 mL/min Analysis
Injection volume: 5 µL Samples: Standard solution and Sample solution
System suitability Calculate the percentage of each individual impurity in the
Sample: Standard solution portion of Alosetron Hydrochloride taken:
Suitability requirements
Tailing factor: NMT 2.0 Result = (rU/rS) × (CS/CU) × (1/F) × 100
Relative standard deviation: NMT 0.73%
Analysis rU = peak response of each impurity from the Sample
Samples: Standard solution and Sample solution solution
Calculate the percentage of alosetron hydrochloride rS = peak response of alosetron from the Standard
(C17H18N4O · HCl) in the portion of Alosetron solution
Hydrochloride taken: CS = concentration of USP Alosetron Hydrochloride RS
in the Standard solution (µg/mL)
Result = (rU/rS) × (CS/CU) × 100 CU = concentration of Alosetron Hydrochloride in the
Sample solution (µg/mL)
rU = peak response from the Sample solution F = relative response factor (see Table 2)
rS = peak response from the Standard solution
CS =concentration of USP Alosetron Hydrochloride RS Acceptance criteria: See Table 2.
in the Standard solution (mg/mL)
CU = concentration of Alosetron Hydrochloride in the
Sample solution (mg/mL)

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Printed on: Wed Feb 08 2023, 11:15:07 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-46606CBE-8631-48D4-BA9A-612EDC69694F_5_en-US
Printed by: Dang Van Vu Official Date: Official as of 01-May-2020 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: md1t3 DOI: https://doi.org/10.31003/USPNF_M1550_05_01
2

Table 2 ADDITIONAL REQUIREMENTS

Relative Relative Acceptance • PACKAGING AND STORAGE: Preserve in tight containers.
Retention Response Criteria, Store between 15° and 30°, protected from light.
Name Time Factor NMT (%) • USP REFERENCE STANDARDS á11ñ
Alosetron 1.0 — — USP Alosetron Hydrochloride RS
USP Alosetron Related Compound A RS
Alosetron related Dealkyl alosetron;
compound A 1.1 1.3 0.15
5-Methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-
Any other individual
—
one.
impurity 1.0 0.10 C12H12N2O 200.24
Total impurities — — 0.8

SPECIFIC TESTS
• WATER DETERMINATION á921ñ, Method I, Method Ia: NMT
1.0%

al
ci
ffi
O

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