Betamethasone
;)
Pregna-1,4-diene-3,20-dione,9-fluoro-11,17,21-trihydroxy-16-methyl-,(11b,16b)-.
9-Fluoro-11b,17,21-trihydroxy-16b-methylpregna-1,4-diene-3,20-dione [378-44-9].
»Betamethasone contains not less than 97.0percent and not more than 103.0percent of C22H29FO5,calculated on the dried basis.
Packaging and storage—
Preserve in tight containers.Store between 2
and 30.
and 30.
Identification—
A:Infrared Absorption á197Mñ.
B:Thin-Layer Chromatographic Identification Test á201ñ—
Test solution—
Prepare a solution of Betamethasone in dehydrated alcohol containing 0.5mg per mL.
Developing solvent system:
a mixture of chloroform and diethylamine (2:1).
Procedure—
Proceed as directed in the chapter,except to locate the spots by lightly spraying with dilute sulfuric acid (1in 2)and heating on a hot plate or under a lamp until spots appear.
Specific rotation á781Sñ:
between +118and +126,calculated on the dried basis.
and +126,calculated on the dried basis.
Test solution:
5mg per mL,in methanol.
Loss on drying á731ñ—
Dry it at 105for 3hours:it loses not more than 1.0%of its weight.
for 3hours:it loses not more than 1.0%of its weight.
Residue on ignition á281ñ:
not more than 0.2%,a platinum crucible being used.
Ordinary impurities á466ñ—
Test solution:
methanol.
Standard solution:
methanol.
Application volume:
10µL.
Eluant:
a mixture of toluene,acetone,methyl ethyl ketone,and formic acid (55:20:20:5),in a nonequilibrated chamber.
Visualization:
5.
Organic volatile impurities,Method Vá467ñ:
meets the requirements,except that the limit for methylene chloride is 0.1%.
Solvent—
Use dimethyl sulfoxide.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of water and acetonitrile (63:37).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Internal standard solution—
Prepare a solution of propylparaben in alcohol having a known concentration of about 0.25mg per mL.
Standard preparation—
Dissolve an accurately weighed quantity of USP Betamethasone RSin alcohol to obtain a solution having a known concentration of about 0.2mg per mL.Transfer 10.0mLof this solution to a suitable vial,and add 10.0mLof Internal standard solution,to obtain a Standard preparationhaving known concentrations of about 0.1mg of betamethasone and about 0.125mg of propylparaben per mL.
Assay preparation—
Using about 80mg of Betamethasone,accurately weighed,prepare as directed for Standard preparation.
Chromatographic system(see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 240-nm detector and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 1.0for betamethasone and 1.4for propylparaben;the resolution,R,between betamethasone and propylparaben is not less than 3.0;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C22H29FO5in the portion of Betamethasone taken by the formula:
800C(RU/RS),
in which Cis the concentration,in mg per mL,of USP Betamethasone RSin the Standard preparation;and RUand RSare the peak height ratios of the betamethasone peak and the internal standard peak 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 242
Pharmacopeial Forum:Volume No.29(5)Page 1427
Phone Number:1-301-816-8139