Granisetron Hydrochloride Tablets
» Granisetron Hydrochloride Tablets contain an amount of Granisetron Hydrochloride equivalent to not less than 92.0 percent and not more than 108.0 percent of the labeled amount of granisetron (C18H24N4O).
Packaging and storage—
Preserve in well-closed containers, protected from light. Store at controlled room temperature.
USP Reference standards 
11
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11—
USP Granisetron Hydrochloride RS
USP Granisetron Related Compound B RS
(N-[(1R,3r,5)-9-Methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide).
(N-[(1R,3r,5)-9-Methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide).
USP Granisetron Related Compound C RS
N-[(1R,3r,5S)-9-Azabicyclo[3.3.1]non-3-yl]-1-methyl-1H-indazole-3-carboxamide.
N-[(1R,3r,5S)-9-Azabicyclo[3.3.1]non-3-yl]-1-methyl-1H-indazole-3-carboxamide.
USP Granisetron Related Compound D RS
1-Methyl-1H-indazole-3-carboxylic acid.
1-Methyl-1H-indazole-3-carboxylic acid.
Identification—
Developing solvent—
Prepare a mixture of methylene chloride, alcohol, water, and ammonium hydroxide (60:40:5:2).
Standard solution—
Dissolve an accurately weighed quantity of USP Granisetron Hydrochloride RS in 0.1 N hydrochloric acid to obtain a solution containing 0.44 mg of granisetron hydrochloride per mL.
Test 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 minutes. Pass through a 0.45-µm filter.
Procedure—
Separately apply 20 µL each of the Standard solution and the Test solution to a suitable thin-layer chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel mixture, dry the spots under a current of warm air for about 5 minutes, 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 minutes, and examine the plate under short-wavelength UV light: the principal spot from the Test solution corresponds in appearance and RF value to that of the Standard solution.
B:
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711—
711—
Medium:
pH 6.5 phosphate buffer, prepared by dissolving 6.8 g of monobasic potassium phosphate in 800 mL of water, adjusting to pH 6.5 with 1 N sodium hydroxide, and diluting to 1 L with water; 500 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Buffer solution pH 2.0, Mobile phase, Diluent, System suitability preparation, and Standard preparation—
Prepare as directed in the Assay.
Standard solution—
Transfer 5.0 mL of the Standard preparation to a 250-mL volumetric flask, and dilute with Diluent to volume.
Test solution—
Pass a portion of the solution under test through a 0.45-µm filter. If necessary, further dilute 5 mL of this solution with Diluent to (5 × L) mL, where L is the Tablet label claim, in mg.
Chromatographic system (see Chromatography 621)—
Prepare as directed in the Assay. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not less than 0.8 and not more than 1.5; and the relative standard deviation for a minimum of six replicate injections is not more than 2.0%.
621)—
Prepare as directed in the Assay. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not less than 0.8 and not more than 1.5; and the relative standard deviation for a minimum of six replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 100 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the amount of C18H24N4O dissolved by the formula:
(312.41 / 348.87)(rU × CS × 500 × D×100) / (rS × L)
in which 312.41 and 348.87 are the molecular weights of granisetron and granisetron hydrochloride, respectively; rU and rS are the peak responses for the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 500 is the volume, in mL, of the Medium; D is the dilution factor of the Test solution; 100 is the conversion factor to percentage; and L is the Tablet label claim, in mg.
Tolerances—
Not less than 75% (Q) of the labeled amount of C18H24N4O is dissolved in 30 minutes.
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Related compounds—
[note—Perform the determination under subdued light and use amber autosampler vials and low-actinic glassware. ]
Buffer solution pH 2.0, Mobile phase, Diluent, System suitability preparation, and Chromatographic system—
Prepare as directed in the Assay.
Standard solution—
Use the Standard preparation, prepared as directed in the Assay.
Test solution—
Use the Assay preparation, prepared as directed in the Assay.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms for at least three times the retention time of the granisetron peak, identify the impurities listed in Table 1, and measure the peak responses. Calculate the percentage of each impurity relative to the labeled content of granisetron in the portion of Tablets taken by the formula:
100(1 / F)(312.41 / 348.87)(CS / CU)(ri / rS)
in which F is the relative response factor as listed in Table 1; 312.41 and 348.87 are the molecular weights of granisetron and granisetron hydrochloride, respectively; CS is the concentration, in mg per mL, of granisetron hydrochloride in the Standard solution; CU is the concentration, in mg per mL, of granisetron in the Test solution, based on the label claim; ri is the peak response of each impurity obtained from the Test solution; and rS is the peak response of the granisetron peak, obtained from the Standard solution. Disregard the peak due to granisetron related compound A that elutes at the relative retention time of about 0.5–0.6, as this impurity is controlled in the drug substance monograph. Not more than 0.7% of granisetron related compound C is found, not more than 1.3% of total specified impurities is found, and not more than 0.5% of any unspecified impurity is found. The reporting level for impurities is 0.1%.
Table 1
| Name | Relative Retention Time | Relative Response Factor (F) | |
|---|---|---|---|
| Granisetron related compound A1 | 0.5–0.6 | — | |
| Granisetron related compound B2 | 0.7 | 0.8 | |
| Granisetron | 1.0 | — | |
| Granisetron related compound C3 | 1.2 | 1.0 | |
| Granisetron related compound D4 | 2.1–2.3 | 1.5 | |
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1
2-Methyl-N-[(1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-2H-indazole-3-carboxamide.
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2
N-[(1R,3r,5S)-9-Methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide.
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3
N-[(1R,3r,5S)-9-Azabicyclo[3.3.1]non-3-yl]-1-methyl-1H-indazole-3-carboxamide.
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4
1-Methyl-1H-indazole-3-carboxylic acid.
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Assay—
[note—Perform the determination under subdued light and use amber autosampler vials and low-actinic glassware. ]
Buffer solution pH 2.0—
Dissolve 15.6 g of monobasic sodium phosphate dihydrate in 900 mL of water, adjust with phosphoric acid to a pH of 2.0, and dilute with water to 1000 mL.
Mobile phase—
Prepare a mixture of Buffer solution pH 2.0, methanol, and tetrahydrofuran (75:24:1.1), mix, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Diluent—
Use Buffer solution pH 2.0.
System suitability preparation—
Dissolve suitable amounts of 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, to obtain a solution having about 0.1 mg of granisetron hydrochloride per mL and about 0.01 mg of each of granisetron related compounds B, C, and D.
Standard preparation—
Dissolve an accurately weighed quantity of USP Granisetron Hydrochloride RS in Diluent to obtain a solution having a known concentration of about 0.11 mg of granisetron hydrochloride per mL.
Assay preparation—
Prepare a solution containing about 0.1 mg of granisetron (base) per mL, based on the label claim, using the following procedure: fill a suitable volumetric flask with Diluent, add 5 Tablets and sonicate for approximately 20 minutes until the Tablets disintegrate completely. Pass a portion of this solution through a 0.45-µm membrane filter, discarding the first few mL.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 300-nm detector, and 4.6-mm × 15-cm column that contains 4-µm polar endcapped packing L1. The flow rate is about 1.2 mL per minute. Chromatograph the System suitability preparation, and identify the components based on the information listed in Table 1. Record the peak responses as directed for Procedure: the column efficiency, determined from the granisetron peak, is not less than 1200 theoretical plates; the tailing factor for the granisetron peak is not less than 0.8 and not more than 1.5; the resolution, R, between the granisetron and granisetron related compound C peaks is not less than 2. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for a minimum of six replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 300-nm detector, and 4.6-mm × 15-cm column that contains 4-µm polar endcapped packing L1. The flow rate is about 1.2 mL per minute. Chromatograph the System suitability preparation, and identify the components based on the information listed in Table 1. Record the peak responses as directed for Procedure: the column efficiency, determined from the granisetron peak, is not less than 1200 theoretical plates; the tailing factor for the granisetron peak is not less than 0.8 and not more than 1.5; the resolution, R, between the granisetron and granisetron related compound C peaks is not less than 2. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for a minimum of six replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, and measure the responses for the major peaks. Calculate the percentage of the labeled amount of granisetron (C18H24N4O) in each Tablet taken by the formula:
100(312.41 / 348.87)(CV / NL)(rU / rS)
in which 312.41 and 348.87 are the molecular weights of granisetron and granisetron hydrochloride, respectively; C is the concentration, in mg per mL, of granisetron hydrochloride in the Standard preparation; V is the volume, in mL, of the Assay preparation, N is the number of Tablets taken to prepare the Assay preparation; L is the Tablet label claim, in mg; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 3375
Pharmacopeial Forum: Volume No. 34(4) Page 937