Dantrolene Sodium Capsules
» Dantrolene Sodium Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of dantrolene sodium (C14H9N4NaO5·3½H2O).
Packaging and storage— Preserve in tight containers.
USP Reference standards 11
USP Dantrolene RS Click to View Structure
USP Dantrolene Related Compound B RS Click to View Structure
5-(4-Nitrophenyl)-2-furaldehyde-2-carboxymethyl semicarbazone.
    C14H12N4O6    
USP Dantrolene Sodium RS Click to View Structure
Identification—
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
Medium: 0.5% methylbenzethonium chloride in water, pH 6.8 (adjusted with 0.1 N potassium hydroxide or 0.1 N hydrochloric acid); 900 mL, deaerated.
Apparatus 1: 100 rpm.
Time: 40 minutes.
Determine the amount of C14H9N4NaO5·3½H2O dissolved by employing the following method.
Standard solution 1 (for Capsules labeled to contain 100 mg) Transfer 25 mg of USP Dantrolene RS, accurately weighed, to a 250-mL volumetric flask. Dissolve in 5.0 mL of dimethylformamide. Add 200 mL of Medium and 10.0 mL of 0.1 N potassium hydroxide. Mix, dilute with Medium to volume, and mix. Pass through a 0.45-µm polytetrafluoroethylene (PTFE) filter, previously wetted with a few drops of isopropyl alcohol, discarding the first 5 mL.
Standard solution 2 (for Capsules labeled to contain 50 mg) Transfer 25.0 mL of Standard solution 1 to a 50-mL volumetric flask containing 0.5 mL of 0.1 N potassium hydroxide. Dilute with Medium to volume, and mix. Pass through a 0.45-µm PTFE filter, previously wetted with a few drops of isopropyl alcohol, discarding the first 5 mL.
Standard solution 3 (for Capsules labeled to contain 25 mg) Transfer 25.0 mL of Standard solution 1 to a 100-mL volumetric flask containing 1.0 mL of 0.1 N potassium hydroxide. Dilute with Medium to volume, and mix. Pass through a 0.45-µm PTFE filter, previously wetted with a few drops of isopropyl alcohol, discarding the first 5 mL.
Test solution— Withdraw 10 mL of the solution under test. Pass through a 0.45-µm PTFE filter, previously wetted with a few drops of isopropyl alcohol. Discard the first 5 mL. Collect the filtered solution in a tube that contains 1 drop of 1 N potassium hydroxide, and mix.
System suitability— [note—All absorbance values should be obtained on solutions within 2 hours of their preparation. ] Using a 0.1-cm cell, measure the absorbance of the Medium, using water as the blank, and measure the absorbance of each of the three Standard solutions using Medium as the blank, at the wavelength of maximum absorbance at about 395 nm. The system is considered suitable for use if the following criteria are met: the absorbance of the Medium is less than 10% of the absorbance of Standard solution 1; the absorbance of Standard solution 2 is between 0.3 and 0.5; and the ratio of the absorbance of Standard solution 1 to that of Standard solution 3 is 4.00 ± 0.10.
Determine the amount of C14H9N4NaO5·3½H2O dissolved by measuring the absorbance of the Test solution at the wavelength of maximum absorbance at about 395 nm in comparison with the appropriate Standard solution, using a 0.1-cm cell and Medium as the blank. All absorbance values are obtained on solutions within 2 hours of their preparation. Calculate the percentage of C14H9N4NaO5·3½H2O dissolved by the formula:
Click to View Image
in which AU and AS are the absorbances obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of dantrolene in the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; 0.79186 is the correction for water of hydration and sodium contained in the dantrolene sodium monohydrate form of the drug, assuming that the bulk drug contains 15% of water and 6.84% of sodium; and LC is the Capsule label claim, in mg.
Tolerances— Not less than 75% (Q) of the labeled amount of C14H9N4NaO5·3½H2O is dissolved in 40 minutes.
Uniformity of dosage units 905: meet the requirements.
Related compounds—
Diluent, Solution A, Solution B, Mobile phase, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Transfer 5 mg, accurately weighed, of USP Dantrolene Related Compound B RS into a 50-mL volumetric flask, and dissolve in 2.5 mL of dimethylformamide. Add 2.5 mL of glacial acetic acid, and dilute with acetone to volume. The final concentration is about 0.1 mg per mL. Quantitatively dilute this solution with Diluent to obtain a solution having a known concentration of about 0.0005 mg per mL of dantrolene related compound B.
Test solution— Use the Assay preparation.
Procedure— Inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of dantrolene related compound B in the portion of Capsules taken by the formula:
100(rU/rS)(CS/CT)
in which rU is the individual peak response for dantrolene related compound B obtained from the Test solution; rS is the response of the corresponding peak in the Standard solution; CS is the concentration, in mg per mL, of dantrolene related compound B in the Standard solution; and CT is the concentration, in mg per mL, of dantrolene sodium in the Test solution: not more than 2% of dantrolene related compound B is found.
Assay—
Diluent— Prepare a solution of acetonitrile and water (70:30).
Buffer solution— Dissolve 3.3 g of ammonium acetate in 1 L of water.
Solution A— Prepare a filtered and degassed mixture of Buffer solution, acetonitrile, and glacial acetic acid (120:76:7).
Solution B— Prepare a filtered and degassed mixture of acetonitrile and water (70:30).
Mobile phase— Use variable mixtures of Solution A and Solution B, as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Use the Standard solution, prepared as directed in the test for Related compounds.
Standard preparation— Transfer 40 mg, accurately weighed, of USP Dantrolene RS to a 50-mL volumetric flask, and dissolve in 2.5 mL of dimethylformamide. Add 2.5 mL of glacial acetic acid, and dilute with acetone to volume. The final concentration is about 0.8 mg per mL. Quantitatively dilute this solution with Diluent to obtain a solution having a known concentration of about 0.08 mg per mL of dantrolene.
Assay preparation— Mix the combined contents of not fewer than 20 Capsules, and transfer an accurately weighed portion, equivalent to the average weight of one Capsule, to a 50-mL volumetric flask. Add 10 mL of dimethylformamide, and sonicate for 15 minutes to dissolve. Add 5 mL of glacial acetic acid, and dilute with acetone to volume. Quantitatively dilute this solution with Diluent to obtain a solution having 0.1 mg per mL of dantrolene sodium, and pass through a 0.45-µm nylon filter.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 365-nm detector and a 4.6-mm ×15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.
Time
(minutes)
Solution A
(%)
Solution B
(%)
Elution
0–8 100 0 isocratic
8–8.1 100®0 0®100 linear gradient
8.1–13 0 100 isocratic
13–13.1 0®100 100®0 linear gradient
13.1–20 100 0 re-equilibration
Separately inject the System suitability solution and the Standard preparation into the chromatograph, record the chromatograms, and measure the peak responses as directed for Procedure: the tailing factor is not more than 1.5; and the relative standard deviation for replicate injections for dantrolene is not more than 1.0%. [note—For the purpose of peak identification, the approximate relative retention times are 0.68 for dantrolene related compound B and 1.0 for dantrolene. ]
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the dantrolene peaks. Calculate the percentage of dantrolene sodium (C14H9N4NaO5·3½H2O) in the portion of Capsules taken by the formula:
100(399.29/314.25)(rU / rS)(CS / CU)
in which 399.29 is the molecular weight of dantrolene sodium; 314.25 is the molecular weight of dantrolene; rU and rS are the peak responses for dantrolene obtained from the Assay preparation and the Standard preparation, respectively; CS is the concentration, in mg per mL, of dantrolene in the Standard preparation; and CU is the concentration, in mg per mL, of dantrolene sodium (C14H9N4NaO5·3½H2O) in the Assay preparation.
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