Nitrofurantoin Oral Suspension
DEFINITION
Nitrofurantoin Oral Suspension is a suspension of Nitrofurantoin in a suitable aqueous vehicle. It contains, in each 100 mL, NLT 460 mg and NMT 540 mg of nitrofurantoin (C8H6N4O5).
IDENTIFICATION
• A. Infrared Absorption
Sample solution:
10 mL of Oral Suspension in 15 mL of acetone
Analysis:
Warm the Sample solution to 50
, with stirring, to coagulate the excipients. Filter, evaporate the acetone with the aid of a warm air blast nearly to dryness, add 10 mL of acetic acid, heat to boiling, and filter while hot. Cool the filtrate to room temperature. Filter the precipitated nitrofurantoin, and dry at 105 for 1 h.
, with stirring, to coagulate the excipients. Filter, evaporate the acetone with the aid of a warm air blast nearly to dryness, add 10 mL of acetic acid, heat to boiling, and filter while hot. Cool the filtrate to room temperature. Filter the precipitated nitrofurantoin, and dry at 105 for 1 h.
Acceptance criteria:
The IR absorption spectrum of a mineral oil dispersion of the precipitate obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Nitrofurantoin RS.
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
Dissolve 6.8 g of monobasic potassium phosphate in 500 mL of water. Add about 30 mL of 1.0 N sodium hydroxide sufficient to adjust to a pH of 7.0, and dilute with water to 1 L.
Mobile phase:
Acetonitrile and Buffer (12:88)
Internal standard solution:
0.065 mg/mL of acetanilide in Mobile phase
Standard stock solution:
0.25 mg/mL of USP Nitrofurantoin RS prepared as follows. Transfer the required amount in suitable volumetric flask, and dissolve in 50% of the final volume of dimethylformamide and 20% of the final volume of water. Cool to room temperature, and dilute with dimethylformamide to volume.
Standard solution:
Transfer 4.0 mL of Standard stock solution to a glass-stoppered flask, and add 15.0 mL of Internal standard solution.
Sample stock solution:
Nominally 0.25 mg/mL of nitrofurantoin prepared as follows. Transfer a volume of Oral Suspension to a suitable volumetric flask, add 20% of the final volume of water, and mix. Add 50% of the final volume of dimethylformamide, and shake the flask for 20 min. Cool to room temperature, and dilute with dimethylformamide to volume. Centrifuge a portion of the solution, and use the supernatant to prepare the Sample solution.
Sample solution:
Transfer 4.0 mL of Sample stock solution to a glass-stoppered flask, add 15.0 mL of Internal standard solution, and mix. Pass a portion of the solution through a 5-µm pore size polytef filter, discarding the first few mL of the filtrate.
Chromatographic system
[Note—Adjust the operating parameters so that the retention time of the nitrofurantoin peak is about 8 min and its peak height is about half-full scale. ]
Mode:
LC
Detector:
UV 254 nm
Column:
3.9-mm × 30-cm; packing L1
Flow rate:
1.2 mL/min
Injection size:
15 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 3.5 between the acetanilide and nitrofurantoin peaks
Relative standard deviation:
NMT 2.0% determined from the ratio of the peak responses
Analysis
Samples:
Standard solution and Sample solution
Calculate the quantity per volume, in mg/100 mL, of the labeled amount of nitrofurantoin (C8H6N4O5) in the Oral Suspension taken:
Result = (RU/RS) × CS × D
| RU | = | = internal standard ratio (peak response of nitrofurantoin/peak response of acetanilide) from the Sample solution |
| RS | = | = internal standard ratio (peak response of nitrofurantoin/peak response of acetanilide) from the Standard solution |
| CS | = | = concentration of USP Nitrofurantoin RS in the Standard solution (mg/mL) |
| D | = | = dilution factor, Sample stock solution to Sample solution, 9500 |
Acceptance criteria:
460–540 mg/100 mL of C8H6N4O5
PERFORMANCE TESTS
• Uniformity of Dosage Units 
905
905
For Oral Suspension packaged in single-unit containers:
Meets the requirements
• Deliverable Volume 698:
698:
For Oral Suspension packaged in multiple-unit containers:
Meets the requirements
IMPURITIES
• Limit of N-(Aminocarbonyl)-N-[([5-Nitro-2- Furanyl]Methylene)-Amino]Glycine (NF 250)
Buffer and Mobile phase:
Prepare as directed in the Assay.
Standard solution:
2.5 µg/mL of USP Nitrofurantoin Related Compound A RS in Mobile phase
Sample solution:
Nominally 0.05 mg/mL of nitrofurantoin in Mobile phase from Oral Suspension. Centrifuge a portion of this solution. Pass a portion of the supernatant through a polytef filter having a 5-µm pore size, discarding the first few mL.
Chromatographic system
[Note—Adjust the operating parameters so that the NF 250 peak has a retention time of between 3 and 6 min and its height is about 0.1 full scale. ]
Mode:
LC
Detector:
UV 375 nm
Column:
3.9-mm × 30-cm; packing L1
Flow rate:
1.2 mL/min
Injection size:
30–60 µL
Analysis
Samples:
Standard solution and Sample solution
Acceptance criteria:
The height of any peak appearing in 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 5.0%).
SPECIFIC TESTS
• pH 791:
4.5–6.5
791:
4.5–6.5
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers.
• USP Reference Standards 11
11
USP Nitrofurantoin RS 
') + '&img=../../images/v35300/cas-67-20-9.gif',600,500);)
USP Nitrofurantoin Related Compound A RS
(N-(Aminocarbonyl)-N-[([5-nitro-2-furanyl]-methylene)-amino]glycine).
(N-(Aminocarbonyl)-N-[([5-nitro-2-furanyl]-methylene)-amino]glycine).
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 4061
Pharmacopeial Forum: Volume No. 35(1) Page 92