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C24H32O4S 416.57
Pregn-4-ene-21-carboxylic acid, 7-(acetylthio)-17-hydroxy-3- oxo-, -lactone, (7,17)-.
17-Hydroxy-7-mercapto-3-oxo-17-pregn-4-ene-21-carboxylic acid -lactone acetate [52-01-7].
» Spironolactone contains not less than 97.0 percent and not more than 103.0 percent of C24H32O4S, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
A: Infrared Absorption 197S
Solution: 1 in 20.
Medium: chloroform.
B: Ultraviolet Absorption 197U
Solution: 10 µg per mL.
Medium: methanol.
Absorptivities at 238 nm, calculated on the dried basis, do not differ by more than 3.0%.
C: Add 100 mg to a mixture of 10 mL of water and 2 mL of 1 N sodium hydroxide, boil the mixture for 3 minutes, cool, and add 1 mL of glacial acetic acid and 1 mL of lead acetate TS: a brown to black precipitate of lead sulfide is formed.
Melting range 741: between 198 and 209, with decomposition. Occasionally it may show preliminary melting at about 135, followed by resolidification.
Specific rotation 781S: between 33 and 37.
Test solution: 10 mg per mL, in chloroform.
Loss on drying 731 Dry it at 105 for 2 hours: it loses not more than 0.5% of its weight.
Limit of mercapto compounds— Shake 2.0 g with 30 mL of water, filter, then to 15 mL of the filtrate add 3 mL of starch TS, and titrate with 0.010 N iodine. Perform a blank determination, and make any necessary correction. Not more than 0.10 mL of 0.010 N iodine is consumed.
Ordinary impurities 466
Test solution: chloroform.
Standard solution: chloroform.
Eluant: butyl acetate.
Visualization: 5.
Organic volatile impurities, Method V 467: meets the requirements.
Solvent— Use dimethyl sulfoxide.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40).
Standard preparation— Dissolve an accurately weighed quantity of USP Spironolactone RS in 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 0.5 mg of USP Spironolactone RS per mL.
Assay preparation— Transfer about 50 mg of Spironolactone, accurately weighed, to a 100-mL volumetric flask, add a mixture of acetonitrile and water (50:50) to volume, and mix.
Chromatographic system (see Chromatography 621)— 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 1 mL per 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 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C24H32O4S in the portion of Spironolactone taken by the formula:
100C(rU / rS),
in which C is the concentration, in mg per mL, of USP Spironolactone RS in the Standard preparation; and rU and rS are the spironolactone peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Andrzej Wilk, Ph.D., Senior Scientific Associate
Expert Committee : (MDCV05) Monograph Development-Cardiovascular
USP29–NF24 Page 2000
Pharmacopeial Forum : Volume No. 29(3) Page 668
Phone Number : 1-301-816-8305