Granisetron Hydrochloride 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

Granisetron Hydrochloride Tablets contain an amount of Granisetron Hydrochloride equivalent to NLT 92.0% and NMT 108.0% of the labeled amount of granisetron (C₁₈H₂₄N₄O).

2 IDENTIFICATION

Delete the following:

A. Thin-Layer Chromatographic Identification Test 〈201〉

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Developing solvent: Prepare a mixture of methylene chloride, alcohol, water, and ammonium hydroxide (60:40:5:2).

Standard solution: 0.44 mg/mL of USP Granisetron Hydrochloride RS in 0.1 N hydrochloric acid

Sample solution: Transfer a number of Tablets, equivalent to about 2 mg of granisetron, to a suitable container. Add 5.0 mL of 0.1 N hydrochloric acid, and sonicate for about 3 min. Pass through a 0.45-µm filter.

Application volume: 20 µL

Analysis

Samples: Standard solution and Sample solution

Dry the spots under a current of warm air for about 5 min, and develop the plate in a paper-lined chromatographic chamber equilibrated with Developing solvent. Allow the chromatogram to develop until the solvent front has moved about 15 cm. Remove the plate, dry the plate under a cold air stream for about 10 min, and examine the plate under short-wavelength UV light.

Acceptance criteria: The principal spot from the Sample solution corresponds in appearance and R_F value to that of the Standard solution. _{(USP 1-May-2021)}

Add the following:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. _{(USP 1- May-2021)}

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

Change to read:

Procedure

[Note—Protect all solutions containing granisetron from light.] _{(USP 1-May-2021)}

Solution A: 15.6 g/L of sodium phosphate monobasic dihydrate in water. Adjust with phosphoric acid to a pH of 2.0, prior to nal dilution. Mobile phase: Methanol, tetrahydrofuran, and Solution A (24: 1.1: 75)

System suitability solution: 0.1 mg/mL of USP Granisetron Hydrochloride RS and 0.01 mg/mL each of USP Granisetron Related Compound B RS, USP Granisetron Related Compound C RS, and USP Granisetron Related Compound D RS in Solution A

Standard solution: 0.11 mg/mL of USP Granisetron Hydrochloride RS in Solution A

Sample solution: Nominally (USP 1-May-2021) 0.1 mg/mL of granisetron (base), based on the label claim, prepared as follows. Fill a suitable volumetric ask with Solution A, add 5 Tablets and sonicate for approximately 20 min until the Tablets disintegrate completely. Pass a portion of this solution through a membrane filter of 0.45-µm pore size, discarding the first few milliliters.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 300 nm. For Identification A, use a diode array detector in the range of 200–400 nm. (USP 1-May-2021) Column: 4.6-mm × 15-cm; 4-µm packing L1

Flow rate: 1.2 mL/min

Injection volume: 20 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

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

Suitability requirements

 (USP 1-May-2021)

Resolution: NLT 2 between the granisetron and granisetron related compound C peaks, System suitability solution Tailing factor: 0.8–1.5 for the granisetron peak, System suitability solution

Relative standard deviation: NMT 2.0% for 6 replicate injections, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of granisetron (C₁₈H₂₄N₄O) in each Tablet taken:

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

r_U = peak response of granisetron from the Sample solution

r_S = peak response of granisetron from the Standard solution

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

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

M_r1 = molecular weight of granisetron, 312.41

M_r2 = molecular weight of granisetron hydrochloride, 348.87

Acceptance criteria: 92.0%–108.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: pH 6.5 phosphate buffer (6.8 g/L of monobasic potassium phosphate in water; adjusted with 1 N sodium hydroxide to a pH of 6.5 prior to nal dilution); 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Solution A and Mobile phase  (USP 1-May-2021) : Prepare as directed in the Assay.

Standard stock solution: Use Standard solution from the Assay.

Standard solution: 0.002 mg/mL of USP Granisetron Hydrochloride RS in Solution A from Standard stock solution Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. If necessary, further dilute 5 mL of this solution with Solution A to (5 × L) mL, where L is the label claim in mg/Tablet.

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

Injection volume: 100 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.8–1.5

Relative standard deviation: NMT 2.0% for 6 replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of granisetron (C₁₈H₂₄N₄O) dissolved:

Result = (r_U /r_S ) × C_S × (M_r1 /M_r2) × V × (1/L) × D × 100

r_U = peak response of granisetron from the Sample solution

r_S = peak response of granisetron from the Standard solution

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

M_r1 = molecular weight of granisetron, 312.41

M_r2 = molecular weight of granisetron hydrochloride, 348.87

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

D = dilution factor for the Sample solution

Tolerances: NLT 75% (Q) of the labeled amount of granisetron (C₁₈H₂₄N₄O is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

[Note—Protect all solutions containing granisetron from light.] _{(USP 1-May-2021)}

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

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 3 times the retention time of the granisetron peak

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of granisetron from the Standard solution

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

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

M_r1 = molecular weight of granisetron, 312.41

M_r2 = molecular weight of granisetron hydrochloride, 348.87

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. Reporting threshold is 0.1%.

Table 1

^a This is a process impurity and should not be included in the total speficied impurities.

^b 2-Methyl-N-[(1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-2H-indazole-3-carboxamide.

^c To be included in total speficied impurities (USP 1-May-2021)

6 ADDITIONAL REQUIREMENTS

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

Change to read:

USP Reference Standards 〈11〉 USP Granisetron Hydrochloride RS USP Granisetron Related Compound B RS

N-[(1R,3r,5S)-9-Methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide.

C₁₇H₂₂N₄O          298.39 (USP 1-May-2021)

USP Granisetron Related Compound C RS

N-[(1R,3r,5S)-9-Azabicyclo[3.3.1]non-3-yl]-1-methyl-1H-indazole-3-carboxamide hydrochloride.

C₁₇H₂₂N₄O ·  HCl               334.85 _{(USP 1-May-2021)}

USP Granisetron Related Compound D RS

1-Methyl-1H-indazole-3-carboxylic acid.

C₉H₈N₂O₂                   176.18 _{(USP 1-May-2021)}