Nitrofurantoin Capsules

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Nitrofurantoin Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of nitrofurantoin (C₈H₆N₄O₅).

2 IDENTIFICATION

A. INFRARED ABSORPTION

Sample: Add 10 ml of 6 N acetic acid to a quantity of the contents of Capsules equivalent to 100 mg of nitrofurantoin. Boil the solution for a few min, and filter while hot. Cool to room temperature, collect the precipitate of nitrofurantoin, and dry at 105° for 1 h.

Acceptance criteria: The IR absorption spectrum of a Mineral oil dispersion of the precipitate so obtained exhibits maxima only at the same wavelength as that of a similar solution of USP Nitrofurantoin RS.

B. The retention time of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: Dissolve 6.8 g of monobasic potassium phosphate in 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, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Solution A (3:22)

Internal standard solution: 1 mg/mL of acetanilide in water

Standard solution: Dissolve 50 mg of USP Nitrofurantoin RS in 40.0 mL of dimethylformamide, and add 50.0 mL of Internal standard solution.

Sample solution: Transfer, as completely as possible, the contents of 20 Capsules to a 500-mL flask. Place the emptied Capsules in a beaker, add 25 mL of dimethylformamide, and agitate for 1 min. Decant into the flask containing the Capsule contents. Rinse the emptied Capsules with another two 25-mL portions of dimethylformamide, and decant into the flask. Add sufficient dimethylformamide to bring the volume to about 250 mL. Insert the stopper in the flask, and shake by mechanical means for 15 min. Dilute with dimethylformamide to volume, and mix. If necessary, the sample may be homogenized using a disperser. Pass through a medium-porosity, sintered-glass filter into a suitable flask. Transfer an aliquot, equivalent to 50 mg of nitrofurantoin, to a flask. Add an accurately measured volume of dimethylformamide to bring the volume in the flask to 40.0 mL. To the flask add 50.0 mL of Internal standard solution, mix, and cool to room temperature. Pass a portion of the solution through a nylon filter of 0.45-µm pore size, discarding the first few mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 30-cm; packing L1

Injection volume: 5-10 µL

System suitability

Sample: Standard solution

[NOTE-Adjust the operating parameters so that the retention time of the nitrofurantoin peak is about 8 min, and the peak heights are about half full-scale.]

Suitability requirements

Resolution: NLT 3.0 between acetanilide and nitrofurantoin

Relative standard deviation: NMT 2.0%, determined from peak response ratios of replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) in the portion of the powder included in the sample aliquot:

                         Result = (R_U/R_S) × (C_S/C_U)

R_U = peak response ratio from the Sample solution

R_S = peak response ratio from the Standard solution 

C_S = concentration of USP Nitrofurantoin RS in the Standard solution (mg/mL)

C_U = nominal concentration of the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1 (where it is labeled as containing nitrofurantoin macrocrystals)

Medium: pH 7.2 (±0.05) phosphate buffer; 900 mL

Apparatus 1: 100 rpm

Times: 1, 3, and 8 h

Standard solution: USP Nitrofurantoin RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary.

Blank: Medium

Instrumental conditions

Mode: UV

Analytical wavelength: 375 nm

Tolerances: See Table 1.

Table 1

The percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the 1-h point conforms to Dissolution (711), Acceptance Table 2 and the percentages dissolved at the 3- and 8-h points conform to the criteria for the final test time in Dissolution (711), Acceptance Table 2.

4.1.2 Test 2 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2

Acid medium: 0.01 N hydrochloric acid for 1 h; 900 mL

pH 7.5 buffer medium: Prepare a pH 7.5 buffer concentrate by dissolving 62.2 g of potassium hydroxide and 129.3 g of monobasic potassium phosphate in water, dilute with water to 1 L, and mix. After 1 h, change the Acid medium to pH 7.5 buffer medium by adding 50 mL of pH 7.5 buffer concentrate, and run for an additional 6 h.

Apparatus 2: 100 rpm, with sinkers made of Teflon-coated steel wire prepared by forming a coil approximately 22 mm long from a 13-cm length of 20-gauge wire (see Figure 1)

Times: 1, 3, and 7 h

Acid-stage standard solution: 0.025 mg/mL of USP Nitrofurantoin RS in Acid medium

Buffer-stage standard solution: 0.075 mg/mL of USP Nitrofurantoin RS in pH 7.5 buffer medium

Instrumental conditions

Mode: UV

Analytical wavelength: 375 nm

Analysis: Calculate the percentages of the labeled amount (Q_i) of nitrofurantoin (C₈H₆N₄O₅) dissolved from UV absorbances at the isosbestic wavelength at about 375 nm on filtered portions of each solution under test, suitably diluted, if necessary, with Acid medium or pH 7.5 buffer medium when appropriate, in comparison with the appropriate Standard solution.

Tolerances: See Table 2.

Table 2

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Table 3.

Table 3

4.1.3 Test 3 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3

Acid medium, pH 7.5 buffer medium, Apparatus 2, Times, Acid-stage standard solution, Buffer-stage standard solution, and Analysis: Proceed as directed in Test 2.

Tolerances: See Table 4.

Table 4

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Dissolution (711). Acceptance Table 2.

4.1.4 Test 4 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4

Acid medium: 0.01 N hydrochloric acid for 1 h; 900 mL, deaerated

pH 7.5 buffer medium: Prepare a pH 7.5 buffer concentrate by dissolving 62.2 g of potassium hydroxide and 129.3 g of monobasic potassium phosphate in water, dilute with water to 1 L, and mix. After 1 h change the Acid medium to pH 7.5 buffer medium by adding 50 mL of pH 7.5 buffer concentrate, and run for an additional 9 h.

Apparatus 2: 100 rpm, with helix sinkers

Times: 1, 3, and 10 h

Standard stock solution: Transfer 25 mg of USP Nitrofurantoin RS to a 10-mL volumetric flask. Add 7.5 mL of dimethylformamide, and sonicate until dissolved. Allow to cool to room temperature, and dilute with dimethylformamide to volume.

Acid-stage standard solution: Dilute 2.0 mL of the Standard stock solution with Acid medium to 200 mL.

Buffer-stage standard solution: Transfer 3.0 mL of the Standard stock solution to a 100-mL volumetric flask, and dilute with pH 7.5 buffer medium to volume.

Stock capsule shell blank: Place 10 empty, clean Capsules into a 900-mL volumetric flask, and add 800 mL of Acid medium. Gently heat to 37 ± 0.5°, and stir until all the Capsules are dissolved. Allow to cool to room temperature, and dilute with Acid medium to volume.

Buffer-stage capsule shell blank: Transfer 100.0 mL of the Stock capsule shell blank to a 1000-mL volumetric flask. Add 56 mL of pH 7.5 buffer medium, dilute with Acid medium to volume, and mix. Filter, using the same filter as for the Sample solution.

Sample solution: Pass portions of the solution under test through a 1.2-µm glass/0.45-µm polyethersulfone combination filter, discarding the first few mL.

Instrumental conditions

Mode: UV

Analytical wavelength: 375 nm

Analysis: Calculate the percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved from portions of the Sample solution in comparison with the appropriate Acid-stage standard solution or Buffer-stage standard solution. Correct for the appropriate capsule shell blank absorbance, using a 0.1-cm cell, and the appropriate medium as the blank.

Tolerances: See Table 5.

Table 5

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Dissolution (711), Acceptance Table 2.

4.1.5 Test 5 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5

Acid medium: 0.01 N hydrochloric acid for 1 h; 900 mL, deaerated

Buffer concentrate: 60 g/L of potassium hydroxide and 129.3 g/L of monobasic potassium phosphate in water

pH 7.5 buffer medium: Prepare by adding 60 mL of Buffer concentrate to 890 mL of Acid medium.

Apparatus 2: 100 rpm, with Teflon-coated sinkers and paddles

Times: 1, 3, and 7 h

Standard stock solution: 2.48 mg/mL of USP Nitrofurantoin RS in acetonitrile. Sonicate using 50% of the final volume of acetonitrile to dissolve. Use an amber volumetric flask.

Acid-stage standard solution: 24.8 µg/mL of USP Nitrofurantoin RS in Acid medium from Standard stock solution. Use an amber volumetric flask.

Buffer-stage standard solution: 74.4 µg/mL of USP Nitrofurantoin RS in pH 7.5 buffer medium from Standard stock solution. Use an amber volumetric flask.

Acid-stage sample solution: After 1 h, collect 10 mL of the solution under test, and pass through a 0.45-µm PVDF filter, discarding the first 5 mL of the filtrate.

Buffer-stage sample solution: After removing 10 ml. of Acid medium, add 60 mL of pH 7.5 buffer medium. The pH of the resulting medium should be about 7.5. Continue the dissolution for another 2 h and 6 h. Collect 10 ml. at each time point, and pass through a 0.45-µm PVDF filter, discarding the first 5 mL of the filtrate.

Acid-stage blank: Use Acid medium.

Buffer-stage blank: Use pH 7.5 buffer medium.

Instrumental conditions

Mode: UV

Analytical wavelength: 375 nm.

Cell: 0.5 cm for acid-stage and 0.1 cm cm for buffer-stage

Analysis

Samples: Acid-stage standard solution, Buffer-stage standard solution, Acid-stage sample solution, Buffer-stage sample solution, Acid-stage blank, and Buffer-stage blank

Calculate the concentration (C) of nitrofurantoin (C₈H₆N₄O₅) in the sample withdrawn from the vessel at each time point (i):

                         Result = (A_U/A_S) × C_S

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL) 

Calculate the percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at each time point (1):

                         Result₁ = C₁ x V₁ x (1/L) x 100

                         Result₂ = [(C₂ x V₂)+ (C₁ x V_S)] x (1/L) x 100

                         Result₃ = {(C₃ x V₃) + [(C₂ + C₁) x V_S]} x (1/L) x 100

C_i = concentration of nitrofurantoin in the portion of sample withdrawn at the specified time point (mg/mL)

V₁ = volume of medium, 900 mL

L = label claim (mg/Capsule)

V₂ = volume of medium, 950 mL

V_S = volume of the Sample solution withdrawn at each time point, 10 mL

V₃ = volume of medium, 940 mL

Tolerances: See Table 6.

Table 6

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Table 7.

Table 7

4.1.6 Test 6 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6

Acid medium: 0.01 N hydrochloric acid; 900 mL

pH 7.5 buffer concentrate: Prepare a pH 7.5 buffer concentrate by dissolving 62.2 g of potassium hydroxide and 129.3 g of monobasic potassium phosphate in water and dilute with water to 1 L.

pH 7.5 buffer medium: 900 mL of Acid medium and 50 mL of pH 7.5 buffer concentrate

Apparatus 2: 100 rpm, with sinkers made of Teflon-coated steel wire prepared by forming a coil approximately 22 mm long from a 13-cm length of 20-gauge wire (see Eigure 1 in Dissolution Test 2)

Times

Acid stage: 1 h

Buffer stage: 3, 4, and 7 h

Acid-stage standard stock solution: 0.11 mg/mL of USP Nitrofurantoin RS in Acid medium prepared as follows. Weigh a suitable amount of USP Nitrofurantoin RS in a volumetric flask and add about 2.5% of the flask volume of N.N-dimethylformamide, Sonicate to dissolve completely. Dilute with Acid medium to final volume.

Acid-stage standard solution: 4.4 µg/mL of USP Nitrofurantoin RS in Acid medium from Acid-stage standard stock solution

Buffer-stage standard stock solution: 0.11 mg/mL of USP Nitrofurantoin RS in pH 7.5 buffer medium prepared as follows. Weigh a suitable amount of USP Nitrofurantoin RS in a volumetric flask and add about 2.5% of the flask volume of N.N-dimethylformamide. Sonicate to dissolve completely. Dilute with pH 7.5 buffer medium to final volume.

Buffer-stage standard solution: 4.4 µg/mL of USP Nitrofurantoin RS in pH 7.5 buffer medium from Buffer-stage standard stock solution

Acid-stage sample solution: Pass portions of the solution under test through a suitable filter and discard the first few mL. Dilute with Acid medium, if necessary.

Buffer-stage sample solution: Pass portions of the solution under test through a suitable filter and discard the first few mL. Dilute with pH 7.5 buffer medium, if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: 375 nm

Dissolution medium: After 1 h in the Acid medium, withdraw 10 mL of the solution under test and add 50 ml. of pH 7.5 buffer concentrate.

Analysis: After 1 h in Acid medium, withdraw 10 mL of solution under test. Add 10 mL of Acid medium, previously warmed to 37 ± 0.5°. Add 50 mL of pH 7.5 buffer concentrate, previously warmed to 37 ± 0.5° and continue the test for 6 h more. At specified times, withdraw 10 mL of solution under test and replace with 10 mL of pH 7.5 buffer medium, previously warmed to 37 ± 0.5°.

Calculate the percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved from portions of the Acid-stage sample solution or Buffer-stage sample solution in comparison with the appropriate Acid-stage standard solution or Buffer-stage standard solution.

Correct for the appropriate capsule shell blank absorbance and the appropriate medium as the blank.

Tolerances: See Table 8.

Table 8

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Dissolution (711), Acceptance Table 2.

4.1.7 Test 7 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7

Acid medium: 0.01 N hydrochloric acid, degassed; 900 mL

Buffer concentrate: 62.2 g/L of potassium hydroxide and 129.3 g/L of monobasic potassium phosphate in water

pH 7.5 buffer medium: Prepare by adding 50 mL of Buffer concentrate to 900 mL of Acid medium. Adjust to pH 7.5 ± 0.05 with 1 N hydrochloric acid or 1 N potassium hydroxide

Apparatus 2: 100 rpm, with Teflon-coated helix sinkers

Times: 1, 3, and 7 h

Standard stock solution: 2.5 mg/mL of USP Nitrofurantoin RS in dimethylformamide. Sonicate to dissolve prior to final dilution.

Acid stage standard solution: 0.025 mg/mL of USP Nitrofurantoin RS in Acid medium from Standard stock solution. Prepare this solution immediately before use by diluting from the Standard stock solution.

Buffer stage standard solution: 0.075 mg/mL of USP Nitrofurantoin RS in pH 7.5 buffer medium from Standard stock solution.

Acid stage sample solution: After 1 h, collect 10 mL of the solution under test, and pass through a suitable filter of 0.45-µm pore size, transferring the first 5 mL of the filtrate back into the dissolution vessel.

Buffer stage sample solution: After removing 10 mL of Acid medium, add 50 mL of pH 7.5 buffer medium. Adjust the pH of the resulting medium to 7.5 ± 0.05 with 1 N hydrochloric acid or 1 N potassium hydroxide, if necessary. Continue collecting 10-mL solution under test at each time point, and pass through a suitable filter of 0.45-um pore size, transferring the first 5 mL of the filtrate back into the dissolution vessel.

Acid stage blank: Use Acid medium.

Buffer stage blank: Use pH 7.5 buffer medium.

Instrumental conditions

Mode: UV

Analytical wavelength: 375 nm

Cell: 0.5 cm for acid stage and 0.1 cm for buffer stage

System suitability

Sample: Acid stage standard solution

Suitability requirement

Relative standard deviation: NMT 2.0%

Analysis

Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, Buffer stage sample solution, Acid stage blank, and Buffer stage blank

Calculate the concentration (C_i) of nitrofurantoin (C₈H₆N₄O₅) in the sample withdrawn from the vessel at each time point (i):

                         Result = (A_U/A_S) × C_S

A_U = absorbance of the Sample solution A

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at each time point (1):

                         Result₁ = C₁ x V₁ x (1/L) x 100

                         Result₂ = [(C₂ x V₂)+ (C₁ x V_S)] x (1/L) x 100

                         Result₃ = {(C₃ x V₃) + [(C₂ + C₁) x V_S]} x (1/L) x 100

C_i = concentration of nitrofurantoin in the portion of sample withdrawn at the specified time point (mg/mL)

V₁= volume of medium, 900 mL.

L = label claim (mg/Capsule)

V₂ = volume of medium, 945 mL 

V_S = volume of the Sample solution withdrawn at each time point, 5 mL 

V₃ = volume of medium, 940 mL

Tolerances: See Table 9.

Table 9

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Dissolution (711), Acceptance Table 2.

4.1.8 Test 8 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 8

Acid medium, pH 7.5 buffer medium, Apparatus 2, Times, Acid-stage standard solution, Buffer-stage standard solution, Instrumental conditions, and Analysis: Proceed as directed in Dissolution Test 2.

Tolerances: See Table 10.

Table 10

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Table 11.

Table 11

4.1.9 Test 9 (where it is labeled as containing nitrofurantoin macrocrystals): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 9

Protect solutions containing nitrofurantoin from light.

Medium: 0.05 M pH 7.2 phosphate buffer (6.8 g/L of potassium phosphate monobasic in water. Adjust with 10% (w/v) sodium hydroxide solution to a pH of 7.2.); 900 mL

Apparatus 1: 100 rpm

Times

For 25-mg strength: 0.5, 1, and 6 h

For 50-mg strength: 1, 3, and 8h

For 100-mg strength: 1, 3, and 12 h

Standard stock solution: 1.1 mg/mL of USP Nitrofurantoin RS prepared as follows. Dissolve a suitable amount of USP Nitrofurantoin RS in about 20% of the flask volume of dimethylformamide. Dilute with Medium to volume.

Standard solution: (L/900) mg/mL of USP Nitrofurantoin RS from Standard stock solution in Medium, where L is the label claim in mg/Capsule

Sample solution: At the times specified, withdraw 10 mL of the solution under test and replace with 10 mL of fresh Medium. Centrifuge a portion of the solution withdrawn and use the supernatant. [NOTE-Centrifuge at 5000 rpm for about 5 min may be suitable.]

Instrumental conditions

Mode: UV

Analytical wavelength: 375 nm

Cell

For 25-mg strength: 0.2 cm

For 50-and 100-mg strength: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of nitrofurantoin (C₈H₆N₄O₅) in the sample withdrawn from the vessel at each time point (i):

                         Result = (A_U/A_S) × C_S

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution A

C_S = concentration of USP Nitrofurantoin RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at each time point (i):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = [(C₂ x V)+ (C₁ x V_S)] x (1/L) x 100

                         Result₃ = {(C₃ x V) + [(C₂ + C₁) x V_S]} x (1/L) x 100

C_i = concentration of nitrofurantoin in the portion of sample withdrawn at time point i (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Capsule)

V_S = volume of the Sample solution withdrawn at each time point and replaced with Medium, 10 mL

Tolerances

For 25-mg strength: See Table 12.

For 50-mg strength: See Table 13.

For 100-mg strength: See Table 14.

Table 12

Table 13

Table 14

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.10 Test 10 (where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms): If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 10

Acid stage medium: 0.01 N hydrochloric acid: 900 mL

Solution A: 62.2 g/L of potassium hydroxide and 129.3 g/L of monobasic potassium phosphate in water

Buffer stage medium: Add 50 ml. of Solution A to 850 mL of Acid stage medium. The pH of this solution is 7.5.

Apparatus 2: 100 rpm, with sinkers made of Teflon-coated steel wire prepared by forming a coil approximately 22 mm long from a 13-cm length of 20-gauge wire

Times

Acid stage: 1 h

Buffer stage: 3 and 7 h. The times in the Buffer stage medium include the time in the Acid stage medium.

Standard stock solution: 0.5 mg/mL of USP Nitrofurantoin RS in dimethylformamide. Sonicate to dissolve.

Acid stage standard solution: 0.01 mg/mL of USP Nitrofurantoin RS from the Standard stock solution in Acid stage medium

Buffer stage standard solution: 0.01 mg/mL of USP Nitrofurantoin RS from the Standard stock solution in Buffer stage medium

Acid stage sample solution: After 1 h, withdraw 50 mL of the solution under test, and pass through a suitable filter of 0.45-µm pore size, discarding the first 4 mL of the filtrate. Dilute with Acid stage medium to a concentration similar to that of the Acid stage standard solution.

Buffer stage sample solution: Add 50 mL of Solution A to the remaining Acid stage medium in the vessel and continue the test. At the specified time points, withdraw a suitable volume of the solution under test and replace with the same volume of Buffer stage medium. Pass through a suitable filter of 0.45-um pore size, discarding the first 4 mL of the filtrate. Dilute with Buffer stage medium to a concentration similar to that of the Buffer stage standard solution.

Acid stage blank: Use Acid stage medium.

Buffer stage blank: Use Buffer stage medium.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 375 nm

Blank: Acid stage medium or Buffer stage medium

Analysis

Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, Buffer stage sample solution, Acid stage blank, and Buffer stage blank

Calculate the concentration (C_i) of nitrofurantoin (C₈H₆N₄O₅) in the sample withdrawn from the vessel at each time point (i):

                         Result_i = (A_U/A_S) × C_S × D

A_U = absorbance from the Acid stage sample solution or Buffer stage sample solution 

A_S = absorbance from the Acid stage stanard solution or Buffer stage standard solution

C_S = 1 concentration of USP Nitrofurantoin RS in the Acid stage standard solution or Buffer stage standard solution (mg/mL)

D = dilution factor for the Acid stage sample solution or Buffer stage sample solution

Calculate the percentage of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at each time point (i):

                         Result₁ = C₁ x V x (1/L) x 100

                         Result₂ = [(C₂ x V)+ (C₁ x V_SA)] x (1/L) x 100

                         Result₃ = [(C₃ x V) + [(C₂ x V_SB) x (C₁ x V_SA)] x (1/L) x 100

C = concentration of nitrofurantoin in the portion of sample withdrawn at time point / (mg/mL)

V = volume of the Acid stage medium or Buffer stage medium, 900 mL

L = label claim (mg/Capsule)

V_SA = volume of the Acid stage sample solution withdrawn at time point 1 and replaced with Solution A, 50 mL

V_SB = volume of the Buffer stage sample solution withdrawn at time point 2 and replaced with Buffer stage medium (mL)

Tolerances: See Table 15.

Table 15

The percentages of the labeled amount of nitrofurantoin (C₈H₆N₄O₅) dissolved at the specified times conform to Table 16.

Table 16

_▲(RB 1-Aug-2023)

Change to read:

4.2 UNIFORMITY OF DOSAGE UNITS (905)

^▲Meet the requirements _{▲(Official 1-Aug-2023)}

Procedure for content uniformity

Solution A, Mobile phase, Internal standard solution, Standard solution, Chromatographic system, and Analysis: Proceed as directed in the Assay.

Sample solution: Transfer the contents of 1 Capsule to a suitable flask, and add a volume of dimethylformamide to obtain a solution having a concentration of about 1.2 mg/mL of nitrofurantoin. Shake the flask for 15 min. If necessary, the sample may be homogenized, using a disperser. In the case of a 50- or 100-mg Capsule, transfer 40.0 mL of this solution to a suitable flask, add 50.0 mL of Internal standard solution, mix, and cool to room temperature. Pass a portion of the solution through a nylon filter of 0.45-µm pore size, discarding the first few mL of the filtrate. In the case of a 25-mg Capsule, transfer 20.0 mL of the solution to a suitable flask, and add 25.0 mL of Internal standard solution instead of 50.0 mL.

^▲_{▲(Official 1-Aug-2023)}

5 IMPURITIES

ORGANIC IMPURITIES: LIMIT OF NITROFURAZONE

Solution A: Prepare as directed in the Assay.

Mobile phase: Tetrahydrofuran and Solution A (1:9)

System suitability stock solution: 5.0 µg/mL each of nitrofurazone and nitrofurantoin in dimethylformamide

System suitability solution: System suitability stock solution and Mobile phase (1:10)

Standard stock solution: 5.0 µg/ml. of USP Nitrofurazone RS in dimethylformamide

Standard solution: Transfer 2.0 mL of the Standard stock solution into a glass-stoppered flask, add 20.0 mL of water, and mix.

Sample solution: Transfer a portion of Capsule contents equivalent to 100 mg of nitrofurantoin into a 25-mL glass-stoppered flask. Add 2.0 mL of dimethylformamide, and shake for 5 min. Add 20.0 mL of water, mix, and allow to stand for 15 min. Pass a portion of the mixture through a nylon filter of 0.45-um pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 375 nm

Column: 3.9-mm x 30-cm; packing L1

Flow rate: 1.6 mL/min

Injection volume: 60-100 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-Adjust the operating parameters so that the nitrofurazone peak in the chromatogram of the Standard solution has a retention time of about 10.5 min and a height of about 0.1 full-scale.]

Suitability requirements

Resolution: NLT 4.0 between the nitrofurazone and nitrofurantoin peaks, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The height of any peak from the Sample solution at a retention time corresponding to that of the main peak from the Standard solution is NMT the height of the main peak from the Standard solution. NMT 0.01% of nitrofurazone is found.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at controlled room temperature.

LABELING: Capsules that contain the macrocrystalline form of nitrofurantoin are so labeled. When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP REFERENCE STANDARDS (11)

USP Nitrofurantoin RS

USP Nitrofurazone RS