Modafinil

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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C₁₅H₁₅NO₂S          273.35

Acetamide, 2-[(diphenylmethyl)sulnyl]-;

2-[(Diphenylmethyl)sulnyl]-acetamide CAS RN: 68693-11-8; UNII: R3UK8X3U3D.

1 DEFINITION

Modafinil contains NLT 98.0% and NMT 101.5% of modafinil (C₁₅H₁₅NO₂S), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A _{(USP 1-May-2021)}

Add the following:

hat of the St B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-May-2021)}

3 ASSAY

Change to read:

PROCEDURE

Buffer: 6.8 g/L of potassium dihydrogen phosphate in water. Adjust with phosphoric acid to a pH of 2.3.

Mobile phase: Acetonitrile and Buffer (35:65)

Diluent: Acetonitrile and water (35:65)

System suitability solution: 5 µg/mL of USP Modafinil RS and 10 µg/mL of USP Salicylic Acid RS in Diluent

Standard solution: 0.1 mg/mL of USP Modafinil RS in Diluent

Sample solution: 0.1 mg/mL of Modafinil in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6mm x 15 = cm; 5-µm packing 11

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: System suitability solution

[NOTE-The relative retention times for modafinil and salicylic acid are about 1.0 and 1.1, respectively.]

Suitability requirements

Resolution: NLT 1.3 between modafinil and salicylic acid

Tailing factor: NMT 1.5 for the modafinil peak

Relative standard deviation: NMT 0.73% _{(USP 1-May-2021)} for the modafinil peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of modafinil (C₁₅H₁₅NO₂S) in the portion of Modafinil taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of modanil from the Sample solution

r_s = peak response of modanil from the Standard solution

C_s = concentration of USP Modanil RS in the Standard solution (mg/mL)

C_u = concentration of Modanil in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–101.5% on the anhydrous basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

Change to read:

ORGANIC IMPURITIES

Buffer, Mobile phase, Diluent, _{(USP 1-May-2021)} System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.05 µg/mL of USP Modafinil RS in Diluent _{(USP 1-May-2021)}

System suitability

Samples: System suitability solution and Sensitivity solution _{(USP 1-May-2021)}

Suitability requirements

Resolution: NLT 1.3 between modafinil and salicylic acid, System suitability solution _{(USP 1-May-2021)}

Tailing factor: NMT 1.5 for the modafinil peak, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution _{(USP 1-May-2021)}

Analysis

Sample: Sample solution

Calculate the percentage of each individual _{(USP 1-May-2021)} impurity in the portion of Modafinil taken:

Result = (r_u /r_T ) × (1/F) × 100

r_u = peak response of each individual impurity

r_T = sum of the responses of all the peaks

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%. _{(USP 1-May-2021)}

Table 1

^a Salicylic acid is used for calculating resolution and is not a potential impurity.

^b 2-[(Diphenylmethyl)sulnyl]acetic acid.

^c 2-[(Diphenylmethyl)sulfonyl]acetamide.

^d 2-[(Diphenylmethyl)sulnyl]acetic acid methyl ester.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.2%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Modanil RS

USP Salicylic Acid RS