Isotretinoin
(eye'' soe tret' i noyn).
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300.44Retinoic acid, 13-cis-.
3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)2-cis-4-trans-6-trans-8-trans-nonatetraenoic acid
[4759-48-2].» Isotretinoin contains not less than 98.0 percent and not more than 102.0 percent of C20H28O2, calculated on the dried basis.
[Caution—Isotretinoin is teratogenic. Avoid inhalation and skin contact.
]
Packaging and storage—
Preserve in tight containers, under an atmosphere of an inert gas, protected from light.
USP Reference standards 
11
—
11—
USP Isotretinoin RS 
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USP Tretinoin RS
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[Note—Avoid exposure to strong light, and use low-actinic glassware in the performance of the following procedures. ]
Identification—
B:
Ultraviolet Absorption 197U—
197U—
Solution:
4 µg per mL.
Medium:
acidified isopropyl alcohol (prepared by diluting 1 mL of 0.01 N hydrochloric acid with isopropyl alcohol to 1000 mL). Absorptivities at 354 nm do not differ by more than 3.0%.
Loss on drying 731—
Dry it in vacuum at room temperature for 16 hours: it loses not more than 0.5% of its weight.
731—
Dry it in vacuum at room temperature for 16 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281:
not more than 0.1%.
281:
not more than 0.1%.
Heavy metals, Method II 231:
0.002%.
231:
0.002%.
Limit of tretinoin—
Mobile phase—
Prepare a suitable filtered and degassed mixture of isooctane, isopropyl alcohol, and glacial acetic acid (99.65:0.25:0.1).
Standard stock solution—
Dissolve an accurately weighed quantity of USP Tretinoin RS in a minimum quantity of methylene chloride, add an amount of isooctane to obtain a solution having a known concentration of about 250 µg per mL, and mix.
Standard solution—
Pipet 1 mL of Standard stock solution into a 100-mL volumetric flask, add isooctane to volume, and mix.
Test solution—
Transfer about 25 mg of Isotretinoin, accurately weighed, to a 100-mL volumetric flask, dissolve in a minimum quantity of methylene chloride, add isooctane to volume, and mix.
System suitability stock solution—
Dissolve a quantity of USP Isotretinoin RS in a minimum amount of methylene chloride, add an amount of isooctane to obtain an isotretinoin concentration of about 250 µg per mL, and mix.
System suitability solution—
Pipet 1 mL of Standard stock solution into a 100-mL volumetric flask, add System suitability stock solution to volume, and mix.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 352-nm detector and a 4.0-mm × 25-cm column containing 5-µm packing L3. The flow rate is about 1 mL per minute. Chromatograph about 20 µL of the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times for isotretinoin and tretinoin are about 0.84 and 1.00, respectively; the resolution, R, between isotretinoin and tretinoin is not less than 2.0; and the relative standard deviation determined from the tretinoin peak response in replicate injections is not more than 2.0%.
621)—The liquid chromatograph is equipped with a 352-nm detector and a 4.0-mm × 25-cm column containing 5-µm packing L3. The flow rate is about 1 mL per minute. Chromatograph about 20 µL of the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times for isotretinoin and tretinoin are about 0.84 and 1.00, respectively; the resolution, R, between isotretinoin and tretinoin is not less than 2.0; and the relative standard deviation determined from the tretinoin peak response in replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of tretinoin by the formula:
10(C / W)(rU / rS)
in which C is the concentration, in µg per mL, of USP Tretinoin RS in the Standard solution; W is the weight, in mg, of Isotretinoin taken; and rU and rS are the tretinoin peak responses obtained from the Test solution and the Standard solution, respectively. The content of tretinoin is not more than 1.0%.
Assay—
Dissolve about 240 mg of Isotretinoin, accurately weighed, in 50 mL of dimethylformamide, add 3 drops of a solution of thymol blue in dimethylformamide (1 in 100), and titrate with 0.1 N sodium methoxide VS to a greenish endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N sodium methoxide is equivalent to 30.04 mg of C20H28O2.
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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3598