Metronidazole Capsules
» Metronidazole Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of metronidazole (C6H9N3O3).
Packaging and storage— Preserve in well-closed, light-resistant containers, and store at controlled room temperature.
USP Reference standards 11
USP Metronidazole RS Click to View Structure
USP Tinidazole Related Compound A RS Click to View Structure
2-Methyl-5-nitroimidazole.
    C4H5N3O2    127.10
Identification—
A: Infrared Absorption 197KThe capsule contents show maxima only at the same wavelengths as those of similarly prepared USP Metronidazole RS, between 1600 cm–1 and 1000 cm–1.
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: 0.1 N hydrochloric acid; 900 mL.
Apparatus 1: 100 rpm.
Time: 30 minutes.
Determine the amount of C6H9N3O3 dissolved using the following procedure.
Standard solution— Accurately weigh a suitable quantity of USP Metronidazole RS into a suitable volumetric flask to obtain a known concentration of about 0.4 mg per mL of metronidazole. Add about 60% of the flask volume of the Medium to the flask, and sonicate to dissolve if necessary. Dilute with Medium to volume.
Test solution— Pass a portion of the solution under test through a nylon filter having a porosity of 0.45 µm, discarding the first few mL.
Procedure— Determine the amount of C6H9N3O3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 278 nm on portions of the Test solution in comparison with the Standard solution, using a 0.05-cm cell and Medium as the blank. Calculate the percentage of C6H9N3O3 dissolved by the formula:
Click to View Image
in which AU and AS are the absorbances obtained with the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of USP Metronidazole RS in the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and L is the Capsule label claim, in mg.
Tolerances— Not less than 85% (Q) of the labeled amount of C6H9N3O3 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Related compounds—
Mobile phase— Prepare as directed in the Assay.
Standard solution— Dissolve suitable quantities of USP Metronidazole RS and USP Tinidazole Related Compound A RS in Mobile phase to obtain a solution having a known concentration of about 0.001 mg per mL of metronidazole and about 0.002 mg per mL of tinidazole related compound A.
Test solution— Use the Assay stock preparation, prepared as directed in the Assay.
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 approximate relative retention times for tinidazole related compound A and metronidazole are about 0.75 and 1.0, respectively; the resolution, R, between tinidazole related compound A and metronidazole is not less than 2.0; the tailing factor is not more than 2.0 for the metronidazole peak; and the relative standard deviation for six replicate injections is not more than 6.0% for both the metronidazole peak and the tinidazole related compound A peak.
Procedure— Separately inject equal volumes (about 30 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for all the peaks. Calculate the percentage of tinidazole related compound A in the portion of Capsules taken by the formula:
100 (CS / CU)(ri / rS)
in which CS is the concentration, in mg per mL, of USP Tinidazole Related Compound A RS in the Standard solution; CU is the nominal concentration of metronidazole, in mg per mL, based on the label claim, in the Assay stock preparation; and ri and rS are the peak responses of tinidazole related compound A obtained from the Test solution and the Standard solution, respectively: not more than 0.1% is found. Calculate the percentage of any unspecified degradation product in the portion of the Capsules taken by the formula:
100 (CS / CU)(ri / rS)
in which CS is the concentration, in mg per mL, of USP Metronidazole RS in the Standard solution; CU is the nominal concentration of metronidazole, in mg per mL, based on the label claim, in the Assay stock preparation; ri is the peak response for any unspecified degradation product peak in the Test solution; and rS is the peak response of metronidazole obtained from the Standard solution: not more than 0.1% of any single unspecified degradation product is found; and not more than 0.5% of total impurities is found.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of water and methanol (4:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed amount of USP Metronidazole RS in Mobile phase to obtain a solution having a known concentration of about 0.03 mg per mL.
Assay stock preparation— Mix the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of metronidazole, to a 100-mL volumetric flask, add 80 mL of Mobile phase, and sonicate for about 10 minutes with intermittent shaking. Shake the flask by mechanical means for 30 minutes. Dilute with Mobile phase to volume, and mix. Centrifuge a portion of the solution. The resulting supernatant has a nominal concentration of 1 mg per mL of metronidazole.
Assay preparation— Quantitatively dilute the Assay stock preparation with Mobile phase to obtain a final solution having a nominal concentration of about 0.03 mg per mL of metronidazole. Pass a portion of this solution through a nylon membrane filter having a porosity of 0.45 µm or finer, discard the first 10 mL of the filtrate, and use the remainder.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 319-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for five replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 30 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms for about twice the retention time of metronidazole, and measure the responses for the metronidazole peak. Calculate the quantity, in percentage based on the label claim, of metronidazole (C6H9N3O3) in the portion of Capsules taken by the formula:
100 (CS / CU)(rU / rS)
in which CS is the concentration, in mg per mL, of USP Metronidazole RS in the Standard preparation; CU is the nominal concentration, in mg per mL, based on the label claim, of metronidazole (C6H9N3O3) in the Assay preparation; and rU and rS are the peak responses 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 Leonel M. Santos, Ph.D.
Senior Scientific Liaison
1-301-816-8168
(SM12010) Monographs - Small Molecules 1
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 3907
Pharmacopeial Forum: Volume No. 34(3) Page 633