Methylpyrrolidone

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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C₅H₉NO 99.1

1-Methyl-2-pyrrolidinone;

N-Methyl-2-pyrrolidone;

N-Methylpyrrolidone;

1-Methyl-2-pyrrolidone;

Pyrrolidin, 1-methyl-2-one-;

1-Methylpyrrolidin-2-one;

N-Methyl-y-butyrolactam;

N-Methyl tetrahydropyrrolone;

1-Methyl-2-oxopyrrolidine;

N-Methyl-1-oxotetramethyleneamine;

2-Methyl-2-azacyclopentanone CAS RN^®: 872-50-4.

1 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197E (CN 1-MAY-2020)

2 IMPURITIES

2.1 ORGANIC IMPURITIES

Standard solution: To 1 mL of USP Methylpyrrolidone RS, add 1 mL of pyrrolidone, and dilute with methylene chloride to 20 mL.

Sample solution: Methylpyrrolidone (neat)

2.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.32-mm x 30-m fused-silica capillary, 5-µm layer of phase G2

Temperatures

Injector: 280°

Detector: 280°

Column: See Table 1.

Table 1

Carrier gas: Nitrogen

Linear velocity: 20 cm/s

Injection type: Split ratio about 100:1

Injection volume: 1 µL

2.3 System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2.0 between pyrrolidone and methylpyrrolidone

2.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity, excluding any solvent peaks and peaks NMT 0.02%, in the portion of Methylpyrrolidone taken:

Result = (r_U/r_T) x 100

r_U = peak response of each individual impurity from the Sample solution

r_T = sum of the responses of all the peaks from the Sample solution

Acceptance criteria: NMT 0.1% of any individual impurity; and NMT 0.3% of total impurities

3 SPECIFIC TESTS

3.1 ALKALINITY

Bromothymol blue solution: Dissolve 50 mg of bromothymol blue in a mixture of 4 mL of 0.02 M sodium hydroxide and 20 mL of alcohol, and dilute with water to 100 mL.

Sample: Methylpyrrolidone (neat)

Analysis: Add 0.5 mL of Bromothymol blue solution as indicator to 50 mL of water, and adjust with 0.02 M potassium hydroxide or 0.02 M hydrochloric acid until a yellow color is obtained. Add 50 mL of the Sample. Titrate with 0.02 M hydrochloric acid to the initial coloration.

Acceptance criteria: NMT 8.0 mL of 0.02 M hydrochloric acid is required.

Change to read:

3.2 CLARITY OF SOLUTION

[NOTE-The Sample is to be compared to the Reference suspension in diffused daylight 5 min after preparation of the Reference suspension.]

Hydrazine solution: 10 mg/mL of hydrazine sulfate. [NOTE-Allow to stand 4-6 h before use.]

Methenamine solution: Transfer 2.5 g of methenamine to a 100-mL glass-stoppered flask, add 25.0 mL of water, insert the glass stopper, and mix to dissolve.

Primary opalescent suspension

[NOTE-This suspension is stable for 2 months, provided it is stored in a glass container free from surface defects. The suspension must not adhere to the glass and must be well mixed before use.]

Transfer 25.0 mL of the Hydrazine solution to the Methenamine solution in the 100-mL glass-stoppered flask. [NOTE-Allow to stand for 24 h.]

Opalescence standard: Transfer 15.0 mL of the Primary opalescent suspension to a 1000-mL volumetric flask, and dilute with water to volume. [NOTE-This suspension should not be used beyond 24 h after preparation.]

Reference suspension: Transfer 5.0 mL of the Opalescence standard to a 100-mL volumetric flask, and dilute with water to volume.

Sample: Methylpyrrolidone (neat)

Analysis: Transfer a sufficient portion of the Sample to a test tube of colorless, transparent, neutral glass with a flat base and an internal diameter of 15-25 mm to obtain a depth of 40 mm. Similarly transfer portions of the Reference suspension and water to separate matching test tubes. Compare the Sample, Reference suspension, and water in diffused daylight, viewing vertically against a black background (see

Visual Comparison (630) (CN 1-May-2019)). [NOTE-The diffusion of light must be such that the Reference suspension can readily be distinguished from water.]

Acceptance criteria: The Sample shows the same clarity as that of water, or its opalescence is not more pronounced than that of the Reference suspension.

Change to read:

3.3 COLOR OF SOLUTION

Comparison solution: Mix 3.0 mL of ferric chloride CS, 3.0 mL of cobaltous chloride CS, and 2.4 mL of cupric sulfate CS with 0.3 N

hydrochloric acid to make 10 mL. Dilute 1.0 mL of this solution with 0.3 N hydrochloric acid to make 100 mL. [NOTE-Prepare and use this solution immediately.]

Sample: Methylpyrrolidone (neat)

Analysis: Transfer a sufficient portion of the Sample to a test tube of colorless, transparent, neutral glass with a flat base and an internal

diameter of 15-25 mm to obtain a depth of 40 mm. Similarly transfer a portion of the Comparison solution to a separate matching test tube. Compare the color of the Sample with that of the Comparison solution in diffused daylight, viewing vertically against a white background (see Visual Comparison (630) (CN 1-May-2019)).

Acceptance criteria: The Sample is not more intensely colored than the Comparison solution.

3.4 WATER DETERMINATION, Method Ic (921)

NMT 0.1%, determined on 1.0 g

4 ADDITIONAL REQUIREMENTS

4.1 PACKAGING AND STORAGE

Preserve in light-resistant containers.

4.2 USP REFERENCE STANDARDS (11)

USP Methylpyrrolidone RS