Triamcinolone Acetonide
;)
Pregna-1,4-diene-3,20-dione,9-fluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-,(11b,16a)-.
9-Fluoro-11b,16a,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with acetone [76-25-5].
»Triamcinolone Acetonide contains not less than 97.0percent and not more than 102.0percent of C24H31FO6,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.Store at 25
,excursions permitted between 15and 30.
,excursions permitted between 15and 30.
Identification—
A:
Infrared Absorption á197Kñ:recrystallized from methanol.
Specific rotation á781Sñ:
between +118and +130.
and +130.
Test solution:
5mg per mL,in dimethylformamide.
Loss on drying á731ñ—
Dry it in vacuum at 60for 4hours:it loses not more than 1.5%of its weight.
for 4hours:it loses not more than 1.5%of its weight.
Heavy metals—
Carefully ignite 1.0g in a muffle furnace at about 550until thoroughly charred.Cool,add to the contents of the crucible 5drops of sulfuric acid and 2mLof nitric acid,cautiously heat until reaction has ceased,then ignite in a muffle furnace at 500to 600until the carbon is entirely burned off.Cool,add 2mLof hydrochloric acid,and slowly evaporate on a steam bath to dryness.Moisten the residue with 1drop of hydrochloric acid and 5mLof hot water,and digest for 2minutes.Add 1drop of phenolphthalein TS,then add 6Nammonium hydroxide dropwise until the reaction is alkaline.Render the solution acid with 1Nacetic acid,then add 1mLof excess,transfer to a beaker,and add water to make 10mL.Pipet 2.5mL(equivalent to 25µg of lead)of Standard Lead Solution(see Lead á231ñ)into a second beaker,add 3mLof water and 1drop of phenolphthalein TS,render just alkaline with 6Nammonium hydroxide,then render acid with 1Nacetic acid,and add 1mLin excess.Dilute with water to 10mL.To each beaker add 5mLof freshly prepared hydrogen sulfide TS,mix,and allow to stand for 5minutes.Pass each solution through a separate,acid-resistant,white,plain membrane filter of 0.22-µm pore size and 25mm in diameter,collecting the precipitates on the filter disks:the color of the precipitate from the solution under test is not darker than that from the control.The heavy metals limit is 0.0025%.
until thoroughly charred.Cool,add to the contents of the crucible 5drops of sulfuric acid and 2mLof nitric acid,cautiously heat until reaction has ceased,then ignite in a muffle furnace at 500to 600until the carbon is entirely burned off.Cool,add 2mLof hydrochloric acid,and slowly evaporate on a steam bath to dryness.Moisten the residue with 1drop of hydrochloric acid and 5mLof hot water,and digest for 2minutes.Add 1drop of phenolphthalein TS,then add 6Nammonium hydroxide dropwise until the reaction is alkaline.Render the solution acid with 1Nacetic acid,then add 1mLof excess,transfer to a beaker,and add water to make 10mL.Pipet 2.5mL(equivalent to 25µg of lead)of Standard Lead Solution(see Lead á231ñ)into a second beaker,add 3mLof water and 1drop of phenolphthalein TS,render just alkaline with 6Nammonium hydroxide,then render acid with 1Nacetic acid,and add 1mLin excess.Dilute with water to 10mL.To each beaker add 5mLof freshly prepared hydrogen sulfide TS,mix,and allow to stand for 5minutes.Pass each solution through a separate,acid-resistant,white,plain membrane filter of 0.22-µm pore size and 25mm in diameter,collecting the precipitates on the filter disks:the color of the precipitate from the solution under test is not darker than that from the control.The heavy metals limit is 0.0025%.
Chromatographic purity—
Mobile phase—
Prepare a filtered and degassed mixture of water and acetonitrile (17:8).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Test solution—
Transfer about 25mg of Triamcinolone Acetonide,accurately weighed,to a 50-mLvolumetric flask;dissolve in acetonitrile;shake vigorously to aid dissolution;dilute with methanol to volume;and mix.
Chromatographic system(see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Test solution,and record the peak responses as directed for Procedure:the resolution,R,between triamcinolone acetonide and any impurity peak is not less than 1.0.
Procedure—
Inject about 20µLof the Test solutioninto the chromatograph,record the chromatogram for not less than four times the retention time of triamcinolone acetonide,and measure all the peak responses.Calculate the percentage of each impurity in the portion of Triamcinolone Acetonide taken by the formula:
100(ri/rs),
in which riis the peak response for each impurity,and rsis the sum of the responses of all the peaks:not more than 0.3%of any individual impurity is found,and not more than 0.8%of total impurities is found.
Assay—
Mobile phase—
Prepare a solution of acetonitrile in water containing approximately 30%(v/v)of acetonitrile.
Internal standard solution—
Dissolve fluoxymesterone in methanol to obtain a solution having a concentration of about 50µg per mL.
Standard preparation—
Dissolve an accurately weighed quantity of USP Triamcinolone Acetonide RSin Internal standard solutionto obtain a solution having a known concentration of about 75µg per mL.Mix an accurately measured volume of the resulting solution with an equal volume of Mobile phaseto obtain a Standard preparationcontaining about 37.5µg of USP Triamcinolone Acetonide RSper mL.
Assay preparation—
Using about 37mg of Triamcinolone Acetonide,accurately weighed,proceed as directed for Standard preparation.
Procedure—
Introduce equal volumes (between 15µLand 25µL)of the Assay preparationand the Standard preparationinto a high-pressure liquid chromatograph (see Chromatography á621ñ)operated at room temperature,by means of a suitable microsyringe or sampling valve.Adjust the operating parameters with Mobile phaseon the column so that the separation of triamcinolone acetonide and internal standard is optimized,with a retention time of about 14.5minutes for triamcinolone acetonide.Typically,the apparatus is fitted with a 4-mm ×30-cm column containing packing L1and is equipped with a UVdetector capable of monitoring absorbance at 254nm,and a suitable recorder.In a suitable chromatogram,the coefficient of variation for five replicate injections of a single specimen is not more than 3.0%;and the resolution factor,R(see Chromatography á621ñ),between the peaks for triamcinolone acetonide and fluoxymesterone is not less than 2.0.Measure the heights of the internal standard and triamcinolone acetonide peaks at the same retention times obtained from the Assay preparationand the Standard preparation.Calculate the quantity,in mg,of C24H31FO6in the portion of Triamcinolone Acetonide taken by the formula:
1000C(RU/RS),
in which Cis the concentration,in mg per mL,of USP Triamcinolone Acetonide RSin the Standard preparation;and RUand RSare the ratios of the peak heights of triamcinolone acetonide to the internal standard obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1959
Pharmacopeial Forum:Volume No.30(3)Page 945
Phone Number:1-301-816-8139