Acitretin Capsules
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 Sample solution preparation. ]
IDENTIFICATION
• Thin-Layer Chromatographic Identification Test 
201
201
Standard solution:
10 mg/mL of USP Acitretin RS in tetrahydrofuran
Sample solution:
Equivalent to 20 mg of acitretin from Capsules. Grind to a fine powder, then triturate for 30 s with 2 mL of tetrahydrofuran. Transfer the suspension to a 12-mL conical centrifuge tube, and centrifuge to obtain a clear supernatant.
Application volume:
10 µL
Developing solvent system:
Chloroform and methanol (4:1)
Analysis
Samples:
Standard solution and Sample solution
Proceed as directed in the chapter, and then air-dry. Spray the plate with a saturated solution of antimony trichloride in chloroform (250 mg/mL) followed by concentrated sulfuric acid, and then locate the spots.
ASSAY
• 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 the 9-cis isomer ]
Sample solution:
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 filtrate. [Note—Inject the Sample solution within 1 h of preparation. ]
Chromatographic system
Mode:
LC
Detector:
UV 365 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
25 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 3.0 between acitretin related compound A and acitretin; NLT 1.8 between the 9-cis isomer and acitretin, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C21H26O3 in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Acitretin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
3% sodium lauryl sulfate in deaerated water, pH 9.6 to 10.0; 900 mL
Apparatus 1:
100 rpm
Time:
30 min
Determine the amount of 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.
Analysis
Samples:
Standard solution, Sample solution, and Capsule shell solution
Analytical wavelength:
347 nm
Cell length:
2 mm
Blank:
Medium
Calculate the amount of C21H26O3 dissolved:
Result = [(AU 
ACS)/AS] × (CS/L) × V × 100
ACS)/AS] × (CS/L) × V × 100| AU | = | = absorbance of the Sample solution |
| ACS | = | = Capsule shell correction, calculated as shown below |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the appropriate Standard solution (mg/mL) |
| L | = | = Capsule label claim (mg) |
| V | = | = volume of Medium (mL), 900 |
The Capsule shell correction, ACS, is calculated as follows:
ACS = ACSS/N
| ACSS | = | = 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 C21H26O3 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure: 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 = (rU/rT) × 100
| rU | = | = peak response for each individual impurity |
| rT | = | = sum of the responses of all the peaks |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|
| Acitretin related compound Aa | 0.84 | 0.5 | |
| Acitretin | 1.0 | — | |
| 9-cis isomerb | 1.09 | — | |
| Any unspecified impurity | — | 0.4 | |
| Total unspecified impurities | — | 0.8 | |
|
a
[(2Z,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid] (C21H26O3 326.43).
b
(E,E,Z,E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed, light-resistant containers.
• USP Reference Standards 11
11
USP Acitretin RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Feiwen Mao, M.S.
Senior Scientific Liaison 1-301-816-8320 |
(SM32010) Monographs - Small Molecules 3 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2072
Pharmacopeial Forum: Volume No. 35(5) Page 1095