Printed on: Fri Jan 05 2024, 09:28:05 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-CC6E908F-AE5A-43AD-BCC6-F4DDBC7A893F_6_en-US

Printed by: USP NF Official Date: Official as of 01-Jun-2023 Document Type: USP & NF @2024 USPC
Do Not Distribute DOI Ref: b57lj DOI: https://doi.org/10.31003/USPNF_M68070_06_01
1

absorption flask add 30 mL of a solution of boric acid (1 in

Povidone 25), 3 drops of bromocresol green-methyl red TS, and
Portions of the monograph text that are national USP text, and sufficient water to immerse the lower end of the condenser
are not part of the harmonized text, are marked with tube. Add 30 mL of a solution of sodium hydroxide (2 in 5)
symbols (◆◆) to specify this fact. through the funnel, rinse the funnel cautiously with 10 mL
of water, immediately close the clamp attached to the
rubber tube, and then start the distillation with steam to
obtain 80–100 mL of the distillate. Remove the absorption
flask from the lower end of the condenser tube, rinsing the
end part with a small quantity of water, and titrate the
distillate with 0.025 mol/L sulfuric acid VS until the color of
the solution changes from green through pale grayish blue
to pale grayish red-purple. Perform a blank determination
in the same manner, and make any necessary correction.
Each milliliter of 0.025 mol/L sulfuric acid VS equals
(C6H9NO)n 0.700 mg of nitrogen.
2-Pyrrolidinone, 1-ethenyl-, homopolymer; Acceptance criteria: 11.5%–12.8% on the anhydrous basis
1-Vinyl-2-pyrrolidinone polymer;
Poly [(2-oxo-1-pyrrolidinyl)ethylene] CAS RN®: 9003-39-8. IMPURITIES
• RESIDUE ON IGNITION á281ñ: NMT 0.1%
DEFINITION
Povidone is a chain polymer of 1-vinyl-2-pyrrolidone. It Change to read:
contains NLT 11.5% and NMT 12.8% of nitrogen (N: 14.01),

al
calculated on the anhydrous basis. It has the nominal K-value • ◆ ▲
LEAD á251ñ, Procedures, Procedure 1▲ (CN 1-Jun-2023)
of NLT 10 and NMT 120. The nominal K-value is shown on Test preparation: 1.0 g in 25 mL of water
the label. Acceptance criteria: NMT 10 ppm◆
• LIMIT OF ALDEHYDES
IDENTIFICATION Solution A: Transfer 8.3 g of potassium pyrophosphate to a
• A. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
Spectroscopy: 197K
Sample: Dry at 105° for 6 h.
Acceptance criteria: Meets the requirements
ci 500-mL volumetric flask and dissolve in 400 mL of water.
Adjust, if necessary, with 1 N hydrochloric acid VS to a pH
of 9.0, and dilute with water to volume.
Solution B: Transfer a quantity of lyophilized aldehyde
• ◆B. dehydrogenase, equivalent to 70 units, to a glass vial, and
Sample solution: 20 mg/mL of Povidone dissolve in 10.0 mL of water. [NOTE—This solution is stable
ffi
Analysis: To 10 mL of the Sample solution, add 20 mL of 1 N for 8 h at 4°.]
hydrochloric acid VS and 5 mL of potassium dichromate TS. Solution C: Transfer 40 mg of nicotinamide adenine
Acceptance criteria: An orange-yellow precipitate is dinucleotide to a glass vial, and dissolve in 10.0 mL of
formed.◆ Solution A. [NOTE—This solution is stable for four weeks at
• ◆C. 4°.]
Solution A: Dissolve 75 mg of cobalt nitrate and 300 mg of Standard solution: Dissolve 0.140 g of acetaldehyde
O

ammonium thiocyanate in 2 mL of water. ammonia trimer trihydrate in water to make 200.0 mL.
Sample solution: 20 mg/mL of Povidone Dilute 1.0 mL of the solution with Solution A to 100.0 mL.
Analysis: Combine Solution A and 5 mL of the Sample Sample solution: 10 mg/mL of Povidone in Solution A.
solution, and render the resulting solution acidic by the Insert a stopper into the flask, heat at 60° for 1 h, and cool
addition of 3 N hydrochloric acid. to room temperature.
Acceptance criteria: A pale blue precipitate is formed.◆ Instrumental conditions
• ◆D. (See Ultraviolet-Visible Spectroscopy á857ñ.)
Sample solution: 5 mg/mL of Povidone Mode: UV
Analysis: To 5 mL of the Sample solution, add a few drops of Analytical wavelength: 340 nm
iodine TS. Cell: 1 cm
Acceptance criteria: A deep red color is produced.◆ Analysis
• E. Samples: Standard solution, Sample solution, and water
Sample solution: 50 mg/mL of Povidone in water Pipet 0.5 mL each of the Standard solution, Sample solution,
Acceptance criteria: The substance dissolves. and water (used for blank test) into separate cells. Add
2.5 mL of Solution A and 0.2 mL of Solution C to each cell.
ASSAY Cover the cells to exclude oxygen. Mix by inversion and
• NITROGEN DETERMINATION allow to stand for 2–3 min at 22 ± 2°. Determine the
Sample: 0.1 g of Povidone absorbances of the solutions using the water as the
Analysis: Weigh the Sample accurately and place in a reference. Add 0.05 mL of Solution B to each cell. Cover
Kjeldahl flask. Add 5 g of a powdered mixture of 33 g of the cells to exclude oxygen. Mix by inversion and allow to
potassium sulfate, 1 g of cupric sulfate, and 1 g of titanium stand for 5 min at 22 ± 2°. Determine the absorbances of
dioxide. Wash down any adhering sample from the neck of the solutions, using the water as the reference.
the flask with a small amount of water. Add 7 mL of sulfuric Calculate the percentage of aldehydes, expressed as
acid allowing it to flow down the inside wall of the flask. acetaldehyde, in the portion of Povidone taken:
Heat the flask gradually until the solution has a clear,
yellow-green color and the inside wall of the flask is free Result = 100 × (CS/CU) × {[(AU2 − AU1) − (AB2 − AB1)]/[(AS2 −
from any carbonized material and then heat for an AS1) − (AB2 − AB1)]}
additional 45 min. After cooling, cautiously add 20 mL of
water, and connect the flask to the distillation apparatus CS = concentration of acetaldehyde in the Standard
previously washed by passing steam through it. To the solution, calculated from the weight of the

https://online.uspnf.com/uspnf/document/1_GUID-CC6E908F-AE5A-43AD-BCC6-F4DDBC7A893F_6_en-US 1/3
Printed on: Fri Jan 05 2024, 09:28:05 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-CC6E908F-AE5A-43AD-BCC6-F4DDBC7A893F_6_en-US
Printed by: USP NF Official Date: Official as of 01-Jun-2023 Document Type: USP & NF @2024 USPC
Do Not Distribute DOI Ref: b57lj DOI: https://doi.org/10.31003/USPNF_M68070_06_01
2

acetaldehyde ammonia trimer trihydrate with the Detector: UV 235 nm

factor 0.72 (mg/mL). Columns
[NOTE—The molar mass of acetaldehyde is Guard: 4.0-mm × 1.0-cm; packing L1
44.05 g/mol, and the molar mass of Analytical: 4.6-mm × 15-cm; 5-µm packing L1
acetaldehyde ammonia trimer trihydrate is Column temperature: 40°
183.26 g/mol. (44.05 × 3)/183.26 = 0.72] Flow rate: 1.0 mL/min
CU = concentration of the Sample solution (mg/mL), Injection volume: 20 µL
calculated on the anhydrous basis System suitability
AU2 = absorbance of the solution from the Sample Samples: System suitability solution and Standard solution
solution, after addition of Solution B Suitability requirements
AU1 = absorbance of the solution from the Sample Resolution: NLT 2.0 between vinylpyrrolidinone and
solution, before addition of Solution B vinyl acetate, in this elution order, System suitability
AB2 = absorbance of the solution from the blank, after solution
addition of Solution B Relative standard deviation: NMT 2.0% of
AB1 = absorbance of the solution from the blank, before vinylpyrrolidinone for six injections, Standard solution
addition of Solution B Analysis
AS2 = absorbance of the solution from the Standard Samples: Standard solution and Sample solution
solution, after addition of Solution B Record the chromatograms and measure the responses for
AS1 = absorbance of the solution from the Standard the vinylpyrrolidinone peak.
solution, before addition of Solution B Calculate the percentage of vinylpyrrolidinone in the
sample taken:
Acceptance criteria: NMT 0.05%
• LIMIT OF HYDRAZINE Result = (rU/rS) × (CS/CU) × 100

al
Standard solution: 9 µg/mL of salicylaldazine in toluene
Sample solution: Transfer 2.5 g to a 50-mL centrifuge tube, rU = peak response of vinylpyrrolidinone from the
add 25 mL of water, and mix to dissolve. Add 500 µL of a Sample solution
solution (1 in 20) of salicylaldehyde in methanol. Swirl and rS = peak response of vinylpyrrolidinone from the
heat in a water bath at 60° for 15 min. Allow to cool and Standard solution
add 2.0 mL of toluene. Insert a stopper in the tube, shake
vigorously for 2 min, and centrifuge. Use the clear upper
toluene layer in the centrifuge tube as the Sample solution.
ci CS

CU
= concentration of vinylpyrrolidinone in the
Standard solution (mg/mL)
= concentration of Povidone in the Sample solution
Chromatographic system (mg/mL), calculated on the anhydrous basis
(See Chromatography á621ñ, General Procedures, Thin-Layer
ffi
Chromatography.) Acceptance criteria: NMT 0.001%
Mode: TLC • 2-PYRROLIDONE
Adsorbent: 0.25-mm layer of dimethylsilanized Mobile phase: Water and methanol (19:1)
chromatographic silica gel with fluorescent indicator Standard solution: 30 µg/mL of 2-pyrrolidinone in Mobile
Application volume: 10 µL phase
Developing solvent system: Methanol and water (2:1) Sample solution: 5 mg/mL of Povidone in Mobile phase
O

Analytical wavelength: UV 365 nm Chromatographic system

Analysis (See Chromatography á621ñ, System Suitability.)
Samples: Standard solution and Sample solution Mode: LC
Proceed as directed in the chapter. Allow the spots to dry, Detector: UV 205 nm
and develop the chromatogram with the Developing Columns
solvent system until the solvent front has moved Guard: 4.0-mm × 1.0-cm; packing L1
three-fourths of the length of the plate. Remove the plate Analytical: 4.6-mm × 15-cm; 5-µm packing L1
from the chamber, mark the solvent front, and allow the Column temperature: 40°
solvent to evaporate. Locate the spots on the plate by Flow rate: 0.8 mL/min
examination under UV light. [NOTE—The retention time of 2-pyrrolidinone is about
Acceptance criteria: Salicylaldazine appears as a fluorescent 7 min.]
spot having an RF value of 0.3; and the fluorescence of any Injection volume: 50 µL
salicylaldazine spot from the Sample solution is not more System suitability
intense than that produced by the spot from the Standard Sample: Standard solution
solution (NMT 1 ppm of hydrazine). Suitability requirements
• VINYLPYRROLIDINONE Column efficiency: NLT 5000 theoretical plates for the
Mobile phase: Water and acetonitrile (90:10) 2-pyrrolidinone peak
System suitability solution: Transfer 10 mg of Symmetry factor: NMT 1.5 for the 2-pyrrolidinone peak
vinylpyrrolidinone and 500 mg of vinyl acetate to a 100-mL Relative standard deviation: NMT 2.0% of
volumetric flask, and dissolve in and dilute with methanol 2-pyrrolidinone for six injections
to volume. Transfer 1.0 mL of this solution to a 100-mL Analysis
volumetric flask, and dilute with Mobile phase to volume. Samples: Standard solution and Sample solution
Standard stock solution: 5 µg/mL of vinylpyrrolidinone in Record the chromatograms and measure the responses for
Mobile phase the 2-pyrrolidinone peak.
Standard solution: 0.25 µg/mL of vinylpyrrolidinone Calculate the percentage of 2-pyrrolidinone in the sample
diluted from the Standard stock solution in Mobile phase taken:
Sample solution: 25 mg/mL of Povidone in Mobile phase
Chromatographic system Result = (rU/rS) × (CS/CU) × 100
(See Chromatography á621ñ, System Suitability.)
Mode: LC rU = peak response of 2-pyrrolidinone from the
Sample solution

https://online.uspnf.com/uspnf/document/1_GUID-CC6E908F-AE5A-43AD-BCC6-F4DDBC7A893F_6_en-US 2/3
Printed on: Fri Jan 05 2024, 09:28:05 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-CC6E908F-AE5A-43AD-BCC6-F4DDBC7A893F_6_en-US
Printed by: USP NF Official Date: Official as of 01-Jun-2023 Document Type: USP & NF @2024 USPC
Do Not Distribute DOI Ref: b57lj DOI: https://doi.org/10.31003/USPNF_M68070_06_01
3

rS = peak response of 2-pyrrolidinone from the rS = peak response of formic acid from the Standard
Standard solution solution
CS = concentration of 2-pyrrolidinone in the Standard CS = concentration of formic acid in the Standard
solution (mg/mL) solution (mg/mL)
CU = concentration of Povidone in the Sample solution CU = concentration of Povidone in the Sample solution
(mg/mL), calculated on the anhydrous basis (mg/mL), calculated on the anhydrous basis

Acceptance criteria: NMT 3.0% Acceptance criteria: NMT 0.5%

• PEROXIDES
Sample solution: 40 mg/mL of Povidone in water, SPECIFIC TESTS
calculated on the anhydrous basis • PH á791ñ
Blank: To 25 mL of the Sample solution, add 2 mL of 13% Sample solution: 50 mg/mL in water
sulfuric acid. Acceptance criteria: 3.0–5.0 for Povidone having a nominal
Instrumental conditions K-value of 30 or less; 4.0–7.0 for Povidone having a nominal
(See Ultraviolet-Visible Spectroscopy á857ñ.) K-value greater than 30
Mode: UV-Vis • WATER DETERMINATION á921ñ, Method I: NMT 5.0%
Analytical wavelength: 405 nm • K-VALUE
Cell: 1 cm Sample solution: Weigh a quantity of undried Povidone,
Analysis equivalent on the anhydrous basis, to the amount
Sample: Sample solution specified in Table 1.
To 25 mL of the Sample solution, add 2 mL of titanium
Table 1
trichloride–sulfuric acid TS, and allow to stand for 30 min.
Measure the absorbance of a portion of this solution Quantity

al
against the Blank. Nominal K-value (g)
Acceptance criteria: NMT 0.35, corresponding to NMT ≤18 5.00
400 ppm, expressed as H2O2
>18 to ≤95 1.00
• FORMIC ACID
Mobile phase: Diluted perchloric acid (1 in 700) >95 0.10
Standard solution: 10 µg/mL of formic acid in water
Sample stock solution: 20 mg/mL of Povidone in water
Sample solution: Transfer a suspension of strongly acidic
ci Dissolve it in 50 mL of water in a 100-mL volumetric flask,
and dilute to volume. Allow to stand for 1 h.
ion-exchange resin (use the hydrogen form of Analysis
ion-exchange resin) in water to a column of about 8 mm in Samples: Sample solution and water
ffi
inside diameter to give a packing depth of about 20 mm in Determine the viscosity of the Sample solution and the
length. Keep the strongly acidic ion-exchange resin layer water, using a capillary-tube viscometer (see Viscosity—
constantly immersed in water. Pour 5 mL of water and Capillary Methods á911ñ), at 25 ± 0.2°.
adjust the flow rate so that water drops at a rate of about Calculate the K-value of Povidone:
1 mL/min. When the level of the water is near the top of
the strongly acidic ion-exchange resin layer, introduce
300� log � + � + 1.5� log � 2 + 1.5� log � − �
O

100 mL of the Sample stock solution into the column. Result =

Disregard the first 2 mL of the eluate, then collect 1.5 mL / 0.15� + 0.003�2
of the solution, and use this as the Sample solution.
Chromatographic system c = weight, on the anhydrous basis, of the specimen
(See Chromatography á621ñ, System Suitability.) tested in each 100.0 mL of solution (g)
Mode: LC z = viscosity of the Sample solution relative to that of
Detector: UV 210 nm water
Column: 7.9-mm × 30-cm; 10-µm packing L17
Column temperature: 35° Acceptance criteria
Flow rate: 1.0 mL/min K-value of Povidone having a stated (nominal) K-value
[NOTE—The retention time of formic acid is about 8 min.] of NMT 15: 85.0%–115.0% of the stated values
Injection volume: 50 µL K-value of Povidone having a stated K-value or a stated
System suitability K-value range with an average of more than 15:
Sample: Standard solution 90.0%–108.0% of the stated value or of the average of
Suitability requirements the stated range
Column efficiency: NLT 1000 theoretical plates for the
formic acid peak ADDITIONAL REQUIREMENTS
Symmetry factor: 0.5–1.5 for the formic acid peak • ◆PACKAGING AND STORAGE: Preserve in tight containers.◆
Relative standard deviation: NMT 2.0% of formic acid • LABELING: Label it to state, as part of the official title, the
for six injections K-value or K-value range of Povidone.
Analysis • ◆USP REFERENCE STANDARDS á11ñ
Samples: Standard solution and Sample solution USP Povidone RS
Record the chromatograms and measure the responses for ◆
the formic acid peak.
Calculate the percentage of formic acid in the sample taken:

Result = (rU/rS) × (CS/CU) × 100

rU = peak response of formic acid from the Sample

solution

https://online.uspnf.com/uspnf/document/1_GUID-CC6E908F-AE5A-43AD-BCC6-F4DDBC7A893F_6_en-US 3/3