Metronidazole
(met'' roe nye' da zole).
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171.151H-Imidazole-1-ethanol, 2-methyl-5-nitro-.
2-Methyl-5-nitroimidazole-1-ethanol
[443-48-1].» Metronidazole contains not less than 99.0 percent and not more than 101.0 percent of C6H9N3O3, calculated on the dried basis.
Packaging and storage—
Preserve in well-closed, light-resistant containers, and store at controlled room temperature.
USP Reference standards 
11
—
11—
USP Metronidazole RS 
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USP Tinidazole Related Compound A RS
2-Methyl-5-nitroimidazole.
C4H5N3O2 127.10
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2-Methyl-5-nitroimidazole.
C4H5N3O2 127.10
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.
Loss on drying 731—
Dry it at 105
for 2 hours: it loses not more than 0.5% of its weight.
731—
Dry it at 105 for 2 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281:
not more than 0.1%.
281:
not more than 0.1%.
Heavy metals, Method II 231:
0.005%.
231:
0.005%.
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—
Dissolve an accurately weighed amount of Metronidazole in Mobile phase to obtain a solution having a known concentration of about 1.0 mg per mL.
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 metronidazole and tinidazole related compound A peaks.
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 metronidazole and tinidazole related compound A peaks.
Procedure—
Separately inject equal volumes (about 30 µL) of the Standard solution and the Test solution into the chromatograph; record the chromatograms for approximately 30 minutes; and measure the peak responses. Calculate the percentage of tinidazole related compound A in the portion of Metronidazole 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 concentration, in mg per mL, of metronidazole in the Test solution; 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 impurity in the portion of Metronidazole 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 concentration, in mg per mL, of metronidazole in the Test solution; 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 impurity is found; and not more than 0.2% 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).
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 preparation—
Dissolve an accurately weighed amount of Metronidazole in Mobile phase to obtain a solution having a known concentration of about 0.03 mg per mL.
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 L7 packing. 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%.
621)—
The liquid chromatograph is equipped with a 319-nm detector and a 4.6-mm × 15-cm column that contains 5-µm L7 packing. 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, of C6H9N3O3 in the portion of Metronidazole 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, of metronidazole 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 |
USP35–NF30 Page 3905
Pharmacopeial Forum: Volume No. 34(3) Page 631