Spironolactone
;)
Pregn-4-ene-21-carboxylic acid,7-(acetylthio)-17-hydroxy-3-oxo-,g-lactone,(7a,17a)-.
17-Hydroxy-7a-mercapto-3-oxo-17a-pregn-4-ene-21-carboxylic acid g-lactone acetate [52-01-7].
»Spironolactone contains not less than 97.0percent and not more than 103.0percent of C24H32O4S,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:Infrared Absorption á197Sñ—
Solution:
1in 20.
Medium:
chloroform.
B:Ultraviolet Absorption á197Uñ—
Solution:
10µg per mL.
Medium:
methanol.
Absorptivities at 238nm,calculated on the dried basis,do not differ by more than 3.0%.
C:
Add 100mg to a mixture of 10mLof water and 2mLof 1Nsodium hydroxide,boil the mixture for 3minutes,cool,and add 1mLof glacial acetic acid and 1mLof lead acetate TS:a brown to black precipitate of lead sulfide is formed.
Melting range á741ñ:
between 198
and 209,with decomposition.Occasionally it may show preliminary melting at about 135,followed by resolidification.
and 209,with decomposition.Occasionally it may show preliminary melting at about 135,followed by resolidification.
Loss on drying á731ñ—
Dry it at 105for 2hours:it loses not more than 0.5%of its weight.
for 2hours:it loses not more than 0.5%of its weight.
Limit of mercapto compounds—
Shake 2.0g with 30mLof water,filter,then to 15mLof the filtrate add 3mLof starch TS,and titrate with 0.010Niodine.Perform a blank determination,and make any necessary correction.Not more than 0.10mLof 0.010Niodine is consumed.
Ordinary impurities á466ñ—
Test solution:
chloroform.
Standard solution:
chloroform.
Eluant:
butyl acetate.
Visualization:
5.
Organic volatile impurities,Method Vá467ñ:
meets the requirements.
Solvent—
Use dimethyl sulfoxide.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of methanol and water (60:40).
Standard preparation—
Dissolve an accurately weighed quantity of USP Spironolactone RSin a mixture of acetonitrile and water (50:50),and quantitatively dilute with the same mixture to obtain a solution having a known concentration of about 0.5mg of USP Spironolactone RSper mL.
Assay preparation—
Transfer about 50mg of Spironolactone,accurately weighed,to a 100-mLvolumetric flask,add a mixture of acetonitrile and water (50:50)to volume,and mix.
Chromatographic system (see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm ×15-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure—
Separately inject equal volumes (about 20µL)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 C24H32O4Sin the portion of Spironolactone taken by the formula:
100C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Spironolactone RSin the Standard preparation;and rUand rSare the spironolactone peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1799
Pharmacopeial Forum:Volume No.29(3)Page 668
Phone Number:1-301-816-8305