Acitretin Capsules

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

Acitretin Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of acitretin (C₂₁H₂₆O₃).

[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. Make all injections within 1 h of the Sample solution preparation.]

2 IDENTIFICATION

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

B. The UV spectrum 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

Diluent: Methanol and tetrahydrofuran (13:10)

Mobile phase: Methanol, alcohol, glacial acetic acid, and water (74:5:0.5:21)

Standard solution: 0.1 mg/mL of USP Acitretin RS in a mixture of Diluent and water (23:2). Dissolve USP Acitretin RS in Diluent equivalent to 80% of the final volume, sonicate for 5 min, add water equivalent to 8% of the final volume, and dilute with Diluent to volume.

System suitability solution: Transfer 2 mL of the Standard solution to a clear 4-mL glass vial. After sealing the vial with a Teflon-lined silicone septum and cap, place the vial on its side in a light chamber, expose it to 400 foot-candles of fluorescent light for 5 min, and then completely wrap the vial with aluminum foil.

[Note—Exposure to the fluorescent light allows for the formation of two degradation products: acitretin related compound A and 6Z-isomer ((2E,4E,6Z,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid).]

Sample solution: Nominally 0.1 mg/mL of acitretin in a mixture of Diluent and water (23:2). Open NLT 20 Capsules, composite the Capsule fill, and mix well. Transfer the Capsule fill to a volumetric flask, add water equivalent to 8% of the final volume to wet the sample, and sonicate for 5 min. Dilute with Diluent to volume, and sonicate for 5 min. Cool to room temperature, pass the suspension through a suitable filter of 0.5-μm pore size, and use the clear ltrate. [Note—Inject the Sample solution within 1 h of preparation.]

3.2 Chromatographic system

Mode: LC

Detector: UV 365 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 25 μL

3.3 System suitability

Samples: Standard solution and System suitability solution

[Note—The relative retention times for acitretin related compound A (2Z-isomer), acitretin, and the 6Z-isomer are 0.84, 1.0, and 1.09,respectively.]

3.4 Suitability requirements

Resolution: NLT 3.0 between acitretin related compound A and acitretin; NLT 1.8 between the 6Z-isomer and acitretin, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of acitretin (C₂₁H₂₆O₃) in the portion of Capsules taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of acitretin from the Sample solution

r_s = peak response of acitretin from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

4.1 Test 1

Medium: 3% sodium lauryl sulfate in deaerated water, pH 9.6–10.0; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Determine the amount of acitretin (C₂₁H₂₆O₃) dissolved using the following method.

Standard solution: Transfer about 14 mg of USP Acitretin RS to a 500-mL volumetric flask. Dissolve in 50 mL of alcohol, and dilute with Medium to volume.

For Capsules labeled to contain 10 mg: Transfer 20 mL of this solution to a 50-mL volumetric flask, and dilute with Medium to volume.

Sample solution: Use portions of the solution under test passed through a suitable filter of 0.45-μm pore size.

Capsule shell solution: Dissolve 6 clean empty-shell Capsules in 900 mL of Medium.

Instrumental conditions

Mode: UV

Analytical wavelength: 347 nm

Cell: 2 mm

Blank: Medium

Analysis

Samples: Standard solution, Sample solution, and Capsule shell solution

Calculate the percentage of the labeled amount of acitretin (C₂₁H₂₆O₃) dissolved:

Result = [(A_u− A_cs)/A_s] × (C_s/L) × V × 100

A_u = absorbance of the Sample solution

A_cs = Capsule shell correction, calculated as shown below

A_s = absorbance of the Standard solution

C_s = concentration of the appropriate Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

The Capsule shell correction, A_cs , is calculated:

A_cs =A_css /N

A_css = absorbance of the Capsule shell solution

N = number of Capsule shells used to prepare the Capsule shell solution

Tolerances: NLT 85% (Q) of the labeled amount of acitretin (C₂₁H₂₆O₃) is dissolved.

4.2 Test 2

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Tier 1

Medium: 3% sodium lauryl sulfate in deaerated water, pH 9.6–10.0 (adjusted with 1 N sodium hydroxide); 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Tier 2

Medium A: Prepare a solution containing pancreatin with NMT 2000 USP Units/L of protease activity in deaerated water, pH 8.0 (adjusted with 1% sodium hydroxide); 450 mL. Use immediately.

Medium B: 6% sodium lauryl sulfate in deaerated water, pH 10.5 (adjusted with 1% sodium hydroxide); 450 mL

Apparatus 1: 100 rpm

Time: 15 min, Medium A; 15 min, Medium A with the addition of Medium B

Determine the amount of acitretin (C₂₁H₂₆O₃) dissolved using the following method.

Mobile phase: Methanol, water, and glacial acetic acid (750:250:1)

Standard stock solution: 280 μg/mL of USP Acitretin RS in absolute alcohol. Use sonication to dissolve.

Standard solution: 20 μg/mL of USP Acitretin RS in Medium under Tier 1, from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable glass filter with 1-μm pore size, discard the first few mL, and use the filtrate for analysis.

Dissolution procedure: Perform the test using the conditions under Tier 1. In the presence of cross-linking repeat the test with new

Capsules using the conditions under Tier 2 as follows. After 15 min, stop the dissolution bath and timer (do not lift the baskets), and add 450 mL of Medium B pre-equilibrated at 37 ± 0.5°. Restart the timer and bath, and after 5 min check the pH of the medium and adjust with 1% sodium hydroxide to a range of 9.6–10.0. Continue dissolution for an additional 10 min.

Chromatographic system

Mode: LC

Detector: 360 nm

Columns

Guard: 4-mm × 1-cm; 5-μm packing L1

Analytical: 4.6-mm × 5-cm; 5-μm packing L1

Temperatures

Autosampler: 40°

Column: 35°

Flow rate: 2.0 mL/min

Injection volume: 10 μL

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 the labeled amount of acitretin (C₂₁H₂₆O₃) dissolved:

Result = (r_u/r_s) × (C_s/L) × V × 100

r_u = peak response of acitretin from the Sample solution

r_s = peak response of acitretin from the Standard solution

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

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 85% (Q) of the labeled amount of acitretin (C₂₁H₂₆O₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities: Limit of Degradation Products

Diluent, Mobile phase, System suitability solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of each degradation product in the portion of Capsules taken:

Result = (r_u/r_T) × 100

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

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

Acceptance criteria: See Table 1.

Table 1

(2Z,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid (C H O 326.43).

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.

Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Acitretin RS