Granisetron Hydrochloride Injection

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

Granisetron Hydrochloride Injection is a sterile solution of Granisetron Hydrochloride in Water for Injection. It contains the equivalent of NLT 93.0% and NMT 107.0% of the labeled amount of granisetron (C₁₈H₂₄N₄O). It may contain suitable preservatives.

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: Methylene chloride, alcohol, ammonium hydroxide, and water (60:40:2:5)

Standard solution: Dissolve USP Granisetron Hydrochloride RS in water or alcohol to obtain a solution having a concentration of granisetron that matches the concentration of granisetron in the Sample solution. To calculate the concentration of granisetron in the Standard solution, use the molecular weights of granisetron (312.41) and granisetron hydrochloride (348.87).

Sample solution: Use the undiluted Injection.

Application volume: Equal volumes of Standard solution and Sample solution, equivalent to 4–5 µg of granisetron 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 before use. Allow the chromatogram to develop until the solvent front has moved about 15 cm. Remove the plate, dry the plate under a current of warm air, 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 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)

Diluent: Methanol and water (25:75)

System suitability solution: 0.1 mg/mL of each USP Granisetron Hydrochloride RS, USP Granisetron Related Compound B RS, USP Granisetron Related Compound C RS, and USP Granisetron Related Compound D RS, in Diluent. Dilute with water to obtain a solution containing about L µg/mL of each component, where L is the labeled amount, in milligrams, of granisetron per milliliter of Injection.

Standard solution: (0.11 × L) mg/mL of USP Granisetron Hydrochloride RS in water, where L is the labeled amount, in milligrams, of granisetron per milliliter of Injection

Sample solution: Use the Injection diluted with water (1:10).

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: 15/L µL, where L is the labeled amount, in milligrams, of granisetron per milliliter of Injection

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

3.2 System suitability

Samples: System suitability solution and Standard solution

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

Suitability requirements

Resolution: NLT 2 between the granisetron and granisetron related compound C peaks, System suitability solution Tailing factor: NMT 3 for the granisetron peak, Standard 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 milliliter of Injection 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: 93.0%–107.0%

4 IMPURITIES

Change to read:

Organic Impurities

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

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

Sample solution: Use the undiluted Injection.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Injection 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 specified 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 specified impurities. (USP 1-May-2021)

5 SPECIFIC TESTS

Change to read:

Bacterial Endotoxins Test 〈85〉: Meets the requirements (USP 1-May-2021)

Sterility Tests 〈71〉: Meets the requirements

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

pH 〈791〉: 4.0–6.0

Other Requirements: Meets the requirements under Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Labeling: It meets the requirements for Labeling 〈7〉, Labels and Labeling for Injectable Products. Label it to indicate the name and the quantity of any added preservative.

Packaging and Storage: Preserve in single-dose or multiple-dose containers, protected from light, and 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)