Tretinoin
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C20H28O2 300.44

Retinoic acid.
all trans-Retinoic acid [302-79-4].
»Tretinoin contains not less than 97.0percent and not more than 103.0percent of C20H28O2,calculated on the dried basis.
Packaging and storage— Preserve in tight containers,preferably under an atmosphere of an inert gas,protected from light.
USP Reference standards á11ñ— USP Isotretinoin RS.USP Tretinoin RS.
NOTE—Avoid exposure to strong light,and use low-actinic glassware in the performance of the following procedures.
Identification—
A: Infrared Absorption á197Mñ.
B: Ultraviolet Absorption á197Uñ—
Solution: 4µg per mL.
Medium: acidified isopropyl alcohol (prepared by diluting 1mLof 0.01Nhydrochloric acid with isopropyl alcohol to 1000mL).
Absorptivities at 352nm,calculated on the dried basis,do not differ by more than 3.0%.
Loss on drying á731ñ— Dry it in vacuum at room temperature for 16hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Limit of isotretinoin—
Mobile phase— Prepare a suitable filtered and degassed mixture of isooctane,isopropyl alcohol,and glacial acetic acid (99.65:0.25:0.1),making adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability solution— Dissolve a quantity of USP Tretinoin RSin a minimum amount of methylene chloride,add a suitable amount of isooctane to obtain a solution having a tretinoin concentration of about 250µg per mL,and mix.
Standard solution— Dissolve an accurately weighed quantity of USP Isotretinoin RSin a minimum quantity of methylene chloride,and add isooctane to obtain a solution having a known concentration of about 250µg per mL.
System suitability preparation— Pipet 5mLof Standard solutioninto a 100-mLvolumetric flask,add System suitability solutionto volume,and mix.
Standard preparation— Pipet 5mLof Standard solutioninto a 100-mLvolumetric flask,add isooctane to volume,and mix.
Test preparation— Transfer about 25mg of Tretinoin,accurately weighed,to a 100-mLvolumetric flask,dissolve in a minimum quantity of methylene chloride,add isooctane to volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 352-nm detector and a 4.0-mm ×25-cm column containing packing L3.The flow rate is about 1mLper minute.Chromatograph about 20µLof System suitability preparation,and record the peak responses.The relative retention times for isotretinoin and tretinoin are about 0.84and 1.00,respectively.The relative standard deviation of the isotretinoin peak response in replicate injections is not more than 2.0%,and the resolution,R,of isotretinoin and tretinoin is not less than 2.0.
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentage of isotretinoin taken by the formula:
10(C/W)(rU/rS),
in which Cis the concentration,in µg per mL,of USP Isotretinoin RSin the Standard preparation,Wis the weight,in mg,of Tretinoin taken,and rUand rSare the peak responses of the isotretinoin peaks obtained from the Test preparationand the Standard preparation,respectively.The content of isotretinoin is not more than 5.0%.
Assay— Dissolve about 240mg of Tretinoin,accurately weighed,in 50mLof dimethylformamide,add 3drops of a 1in 100solution of thymol blue in dimethylformamide,and titrate with 0.1Nsodium methoxide VSto a greenish endpoint.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nsodium methoxide is equivalent to 30.04mg of C20H28O2.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 1956
Phone Number:1-301-816-8389
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