Methoxsalen

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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C₁₂H₈O₄ 216.19

7H-Furo[3,2-g][1]benzopyran-7-one, 9-methoxy-;

9-Methoxy-7H-furo[3,2-g][1]benzopyran-7-one;

9-Methoxy-7H-furo[3,2-g]chromen-7-one CAS RN®: 298-81-7.

1 DEFINITION

Methoxsalen contains NLT 98.0% and NMT 102.0% of methoxsalen (C₁₂H₈O₄ ), calculated on the anhydrous basis.

[Caution—Avoid contact with the skin.]

2 IDENTIFICATION

Change to read:

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

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

3.1 Procedure

Mobile phase: Acetonitrile and water (35:65)

Standard stock solution: 0.2 mg/mL of USP Methoxsalen RS in alcohol

Standard solution: 4 μg/mL of USP Methoxsalen RS in Mobile phase from the Standard stock solution

Sample stock solution: 0.2 mg/mL of Methoxsalen in alcohol

Sample solution: 4 μg/mL of Methoxsalen in Mobile phase from the Sample stock solution

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 30-cm; packing L1; or 3.9-mm × 30-cm; 10-μm packing L1; or 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methoxsalen (C₁₂H₈O₄) in the portion of Methoxsalen taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of methoxsalen from the Sample solution

r_S = peak response of methoxsalen from the Standard solution

C_S = concentration of USP Methoxsalen RS in the Standard solution (μg/mL)

C_U = concentration of Methoxsalen in the Sample solution (μg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉

Sample: 1 g

Acceptance criteria: NMT 0.1%

4.1 Organic Impurities

Solution A: 6% tetrahydrofuran in water

Solution B: Methanol

Solution C: Solution A and methanol (60:40)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (1:1)

System suitability solution: 0.05 mg/mL each of USP Methoxsalen Related Compound A RS and USP Methoxsalen Related Compound B RS in Diluent Standard stock solution: 1.0 mg/mL of USP Methoxsalen RS in Diluent

Standard solution: 1.0 μg/mL of USP Methoxsalen RS in Diluent from the Standard stock solution

Sensitivity solution: 0.5 μg/mL of USP Methoxsalen RS in Diluent from the Standard solution

Sample solution: 1.0 mg/mL of Methoxsalen in Diluent

4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 247 nm

Column: 4.6-mm × 25-cm; 5-μm packing L11

Flow rate: 1.2 mL/min

Injection volume: 20 μL

4.3 System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

4.4 Suitability requirements

Resolution: NLT 1.0 between methoxsalen related compound A and methoxsalen related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Methoxsalen taken:

Result = (r_U/r_S)x(C_S/C_U ) × (1/F) × 100

r_U = peak area of each impurity from the Sample solution

r_S = peak area of methoxsalen from the Standard solution

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

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

F = relative response factor for each individual impurity (see Table 2)

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Methoxsalen RS

USP Methoxsalen Related Compound A RS

4-Methoxy-7H-furo[3,2-g]chromen-7-one.

C₁₂H₈O₄216.19

USP Methoxsalen Related Compound B RS

4,9-Dimethoxy-7H-furo[3,2-g]chromen-7-one.

C₁₃H₁₀O₅ 246.22