Packaging and storage—
Preserve in tight, light-resistant containers.
Labeling—
Label it to indicate whether it is anhydrous or hydrous. Nitrofurantoin in the form of macrocrystals is so labeled. The labeling states the specific surface area and which method, specified under
Specific Surface Area 
846
, is used.
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.
Water, Method III 921—
Dry it at 140
for 30 minutes: the anhydrous form loses not more than 1.0%, and the hydrous form between 6.5% and 7.5%, of its weight.
Specific surface area 846 (where it is labeled as being in the form of macrocrystals)—
Outgas a portion of the powder to be placed under test at 150
for 10 minutes at ambient pressure with nitrogen: the limits are between 0.045 m
2 per g and 0.20 m
2 per g.
Limit of nitrofurfural diacetate—
In a 10-mL volumetric flask dissolve 100 mg of Nitrofurantoin in 1 mL of dimethylformamide, add acetone to volume, and mix. Apply 10 µL of this solution and 10 µL of a Standard solution of
USP Nitrofurfural Diacetate RS in a 1 in 10 mixture of dimethylformamide in acetone containing 100 µg per mL to a suitable thin-layer chromatographic plate (see
Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of chloroform and methanol (9:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, allow it to air-dry for 5 minutes, and heat the plate at 105
for 5 minutes. Remove the plate from the oven and, while it is still warm, locate the spots by spraying the plate with a solution prepared by dissolving 0.75 g of phenylhydrazine hydrochloride in 50 mL of water, decolorizing with activated charcoal, adding 25 mL of hydrochloric acid, and mixing with water to produce 200 mL. Any spot produced by the test specimen, at an
RF value of about 0.7, is not greater in size or intensity than that produced by the Standard solution at the same
RF value: not more than 1.0% of nitrofurfural diacetate is found.
Limit of nitrofurazone—
pH 7.0 Phosphate buffer—
Prepare as directed in the Assay.
Mobile phase—
Prepare a filtered and degassed mixture of pH 7.0 Phosphate buffer and tetrahydrofuran (9:1).
Standard preparation—
Prepare a solution of
USP Nitrofurazone RS in dimethylformamide containing 5.0 µg per mL. Pipet 2 mL of this solution into a glass-stoppered flask, add 20.0 mL of water, and mix.
Test preparation—
Dissolve 100 mg of Nitrofurantoin in 2.0 mL of dimethylformamide in a glass-stoppered, 25-mL flask. Add 20.0 mL of water, mix, and allow to stand for about 15 minutes to allow precipitate to form. Pass a portion of the solution through a nylon filter having a 0.45-µm porosity, and use the clear filtrate.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 375-nm detector and a 3.9-mm × 30-cm column containing packing L1. The flow rate is about 1.6 mL per minute. Chromatograph the
Standard preparation, adjusting the operating parameters so that the nitrofurazone peak has a retention time of about 10.5 minutes and its height is about 0.1 full-scale. The relative standard deviation determined from the peak height in replicate injections is not more than 2.0%. Prepare a solution containing about 5.0 µg each of nitrofurazone and nitrofurantoin per mL in dimethylformamide. Dilute this solution 1:10 with
Mobile phase, and inject 60 µL to 100 µL: the resolution,
R, of the two peaks is not less than 4.0.
Procedure—
Separately inject equal volumes (60 µL to 100 µL) of the Standard preparation and the Test preparation into the chromatograph, and record the chromatograms. The height of any peak appearing in the chromatogram of the Test preparation at a retention time corresponding to that of the main peak from the Standard preparation is not greater than the height of the main peak from the Standard preparation: not more than 0.01% of nitrofurazone is found.
Assay—
pH 7.0 Phosphate buffer—
Dissolve 6.8 g of monobasic potassium phosphate in about 500 mL of water. Add a volume of 1.0 N sodium hydroxide (about 30 mL) sufficient to adjust to a pH of 7.0, dilute with water to 1 liter, and mix.
Mobile phase—
Prepare a filtered and degassed mixture of pH 7.0 Phosphate buffer and acetonitrile (88:12).
Internal standard solution—
Prepare a solution containing about 1 mg of acetanilide per mL in water, and mix.
Standard preparation—
Dissolve about 50 mg of
USP Nitrofurantoin RS, accurately weighed, in 40.0 mL of dimethylformamide in a glass-stoppered flask, add 50.0 mL of
Internal standard solution, and mix.
Assay preparation—
Using about 50 mg of Nitrofurantoin, accurately weighed, proceed as directed for Standard preparation.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1. Chromatograph the
Standard preparation, adjusting the operating parameters so that the retention time of the nitrofurantoin peak is about 8 minutes and the peak heights are about half full-scale. The resolution,
R, between acetanilide and nitrofurantoin is not less than 3.0, and the relative standard deviation determined from the ratio of the peak responses in replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (5 µL to 10 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C
8H
6N
4O
5 in the portion of Nitrofurantoin taken by the formula:
W(RU / RS),
in which
W is the weight, in mg, of
USP Nitrofurantoin RS in the
Standard preparation; and
RU and
RS are the peak response ratios obtained from the
Assay preparation and the
Standard preparation, respectively.
;)
