Meprobamate

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

Meprobamate contains NLT 97.0% and NMT 101.0% of meprobamate (C₉H₁₈N₂O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample: 1 mg in 200 mg

Acceptance criteria: The IR absorption spectrum of a potassium bromide dispersion of the Sample, previously dried, exhibits maxima only at the same wavelengths as that of a similar preparation of USP Meprobamate RS. If a difference appears, dissolve portions of both the

Sample and the Reference Standard in acetone at a concentration of 8 mg/mL. Dilute 0.1-mL portions of the acetone solutions with 1 mL of n-heptane, and remove the solvents by evaporation under nitrogen at a temperature of 30°. Dry the residues under vacuum at room temperature for 30 min, and repeat the test on the residues.

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

3 ASSAY

Procedure

Mobile phase: Acetonitrile and water (30:70)

Standard solution: 5 mg/mL of USP Meprobamate RS prepared as follows. Dissolve the Standard first in acetonitrile using 30% of final volume. Sonicate if necessary to dissolve, and cool to room temperature. Dilute with water to volume.

Sample solution: 5 mg/mL of Meprobamate prepared as follows. Dissolve the sample first in acetonitrile using 30% of final volume. Sonicate if necessary to dissolve, and cool to room temperature. Dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 200 nm

Column: 4.6-mm × 25-cm; 4-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: 2 times the retention time of meprobamate

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of meprobamate (C₉H₁₈N₂O₄) in the portion of Meprobamate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 97.0%–101.0% on the dried basis

4 IMPURITIES

Organic Impurities: Procedure 1

Standard solutions: Dissolve USP Meprobamate RS in alcohol, and mix to obtain Standard solution A with a known concentration of 1.0 mg/mL. Dilute quantitatively with alcohol to the obtain the Standard solutions with the compositions given in Table 1.

Table 1

Sample solution: 100 mg/mL of Meprobamate in alcohol

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: Thin-layer chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel

Application volume: 2 μL

Developing solvent system: Hexane, acetone, and pyridine (70:30:10)

Spray reagent: 5 mg/mL of vanillin in a cooled mixture of sulfuric acid and alcohol (80:20)

Analysis

Samples: Standard solutions and Sample solution

Position the plate in a chromatographic chamber, and develop the chromatograms in the Developing solvent system 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, and air-dry the plate for 15 min. Heat the plate at 100° for 15 min, cool, and spray with Spray reagent. Heat the plate at 110° for 15–20 min, cool, and allow the plate to develop blue-purple spots at room temperature. [Note—Color development requires about 30–60 min.]

Examine the plate, and compare the intensities of any secondary spots of the Sample solution with those of the principal spots of the Standard solutions.

Acceptance criteria: No secondary spot of the Sample solution is larger or more intense than the principal spot of Standard solution A (1.0%), and the sum of the intensities of all secondary spots of the Sample solution corresponds to NMT 2.0%.

Organic Impurities, Procedure 2: Limit of Methyl Carbamate

Standard solution: 1.0 mg/mL of methyl carbamate

Sample solution: Transfer 1.0 g of finely powdered Meprobamate to a beaker, add 5.0 mL of water, and stir to wet the powder completely.

Filter the slurry through a small plug of glass wool in the stem of a glass funnel. Use the clear filtrate.

Mobile phase: Water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 200 nm

Column: 3.9–4.6-mm × 25–30-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The peak response of the Sample solution is not greater than that of the Standard solution, corresponding to NMT 0.5% of methyl carbamate.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry a sample under vacuum at 60° for 3 h.

Acceptance criteria: NMT 0.5%

Melting Range or Temperature 〈741〉: 103°–107°, but the range between the beginning and end of melting is NMT 2°.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Meprobamate RS