Acitretin

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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C₂₁H₂₆O₃326.43
2,4,6,8-Nonatetraenoic acid, 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-, (all-E)-;
(all-E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid CAS RN®: 55079-83-9; UNII: LCH760E9T7.

1 DEFINITION

Acitretin contains NLT 98.0% and NMT 102.0% of C₂₁H₂₆O₃, calculated on the dried basis.

[Caution - Acitretin is a teratogen. Great care should be taken when handling to avoid inhalation of dust or contact with skin.]

[Note - Use low-actinic glassware and perform all tests under yellow and subdued light.]

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 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

[Note - Store the solutions at 4° before injection.]

Mobile phase: Alcohol, glacial acetic acid, and water (92:0.3:8)

System suitability stock solution: 0.01 mg/mL each of USP Acitretin RS and USP Tretinoin RS in alcohol. [Note - Dissolve in tetrahydrofuran before diluting with alcohol.]

System suitability solution: 0.25 μg/mL each of USP Acitretin RS and USP Tretinoin RS in alcohol, from System suitability stock solution

Standard solution: 0.1 mg/mL of USP Acitretin RS in alcohol. [Note—Dissolve in tetrahydrofuran before diluting with alcohol. The finalconcentration of tetrahydrofuran in the preparation will be 2%.]

Sample stock solution: 0.25 mg/mL of Acitretin in tetrahydrofuran and alcohol (1:19). [Note—Dissolve in tetrahydrofuran before diluting with alcohol.]

Sample solution: 0.1 mg/mL of Acitretin in alcohol, from Sample stock solution

3.2 Chromatographic system

Mode: LC

Detector: UV 360 nm

Column: 4-mm × 25-cm; packing L1

Flow rate: 0.6 mL/min

Injection size: 10 μL

3.3 System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for tretinoin and acitretin are 0.84 and 1.0, respectively.]

3.4 Suitability requirements

Resolution: NLT 2.0 between tretinoin and acitretin, System suitability solution

Relative standard deviation: NMT 1.0% of acitretin, Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₁H₂₆O₃ in the portion of Acitretin 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 Acitretin RS in the Standard solution (mg/mL)

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

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

4 IMPURITIES

4.1 Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

4.2 Organic Impurities

[Note—Store the solutions at 4° before injection.]

4.3 Procedure

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.8 μg/mL each of USP Acitretin RS, USP Acitretin Related Compound A RS, and USP Acitretin Related Compound B RS in alcohol. [Note-Dissolve in tetrahydrofuran before diluting with alcohol.]

Sample solution: 0.25 mg/mL of Acitretin in tetrahydrofuran and alcohol (1:19). [Note—Dissolve in tetrahydrofuran before diluting withalcohol.]

4.4 System suitability

Sample: Standard solution

4.5 Suitability requirements

Resolution: NLT 1.5 between acitretin related compound A and acitretin; NLT 1.5 between acitretin related compound B and acitretin

Relative standard deviation: NMT 10.0% for acitretin related compound A and NMT 10.0% for acitretin related compound B

4.6 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of acitretin related compound A and acitretin related compound B in the portion of Acitretin taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response from the relevant impurity from the Sample solution

r_s = peak response from the relevant impurity from the Standard solution

C_s = concentration of USP Acitretin Related Compound A RS or USP Acitretin Related Compound B RS in the Standard solution (μg/mL)

C_u = concentration of Acitretin in the Sample solution (μg/mL)

Calculate the percentage of impurities other than acitretin related compounds A and B in the portion of Acitretin taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each individual unspecified impurity from the Sample solution

r_s = peak response of USP Acitretin RS in the Standard solution

C_s = concentration of USP Acitretin RS in the Standard solution (μg/mL)

C_u = concentration of Acitretin in the Sample solution (μg/mL)

4.7 Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 1.0%

Impurity Table 1

5 SPECIFIC TESTS

Loss on Drying 〈731〉: Dry a sample in a vacuum at a pressure not exceeding 19 mm of mercury at 100° for 4 h: it loses NMT 0.2% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Acitretin RS

USP Acitretin Related Compound A RS

(2Z,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid.

C₂₁H₂₆O₃ 326.43

USP Acitretin Related Compound B RS

Ethyl (all-E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoate.

C₂₃H₃₀O₃ 354.48

USP Tretinoin RS