Docusate Sodium
C20H37NaO7S 444.56

Butanedioic acid, sulfo-, 1,4-bis(2-ethylhexyl) ester, sodium salt.
Sodium 1,4-bis(2-ethylhexyl) sulfosuccinate [577-11-7].
» Docusate Sodium contains not less than 99.0 percent and not more than 100.5 percent of C20H37NaO7S, calculated on the anhydrous basis.
Packaging and storage— Preserve in well-closed containers.
Clarity of solution— Dissolve 25 g in 100 mL of alcohol: the solution does not develop a haze within 24 hours.
Identification— Place a small piece of it on a salt plate, add 1 drop of acetone, and promptly cover with another salt plate. Rub the plates together to dissolve the specimen, slide the plates apart, and allow the acetone to evaporate: the IR absorption spectrum of the film so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Docusate Sodium RS.
Water, Method I 921: not more than 2.0%.
Residue on ignition 281: between 15.5% and 16.5%, calculated on the anhydrous basis.
Heavy metals 231 Transfer 2.0 g to a platinum crucible, and ignite until free from carbon. Cool, moisten the residue with 1 mL of hydrochloric acid, and evaporate on a steam bath to dryness. Add 2 mL of 6 N acetic acid, digest on a steam bath for 5 minutes, filter into one of a pair of matched 50-mL color-comparison tubes, and wash the residue with sufficient water to make 25 mL: the limit is 0.001%.
Limit of bis(2-ethylhexyl) maleate—
Mobile phase— Prepare a filtered and degassed mixture of alcohol and water (78:22). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Dissolve an accurately weighed quantity of USP Bis(2-ethylhexyl) Maleate RS in alcohol, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 80 µg per mL.
Test solution— Transfer about 1.0 g of Docusate Sodium, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with alcohol to volume, and mix. If necessary, warm the mixture using the steam bath to achieve a complete dissolution.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm× 3-cm column that contains 3.5-µm packing L1. The column temperature is maintained at 30. The flow rate is about 1.0 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 3 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the bis(2-ethylhexyl) maleate peaks. Calculate the percentage of bis(2-ethylhexyl) maleate in the portion of Docusate Sodium taken by the formula:
5C/W(rU / rS)
in which C is the concentration, in µg per mL, of USP Bis(2-ethylhexyl) Maleate RS in the Standard solution; W is the weight, in mg, of Docusate Sodium taken to prepare the Test solution; and rU and rS are the peak responses of bis(2-ethylhexyl) maleate obtained from the Test solution and the Standard solution, respectively: not more than 0.4% is found.
Tetra-n-butylammonium iodide solution— Transfer 1.250 g of tetra-n-butylammonium iodide to a 500-mL volumetric flask, dilute with water to volume, and mix.
Salt solution— Transfer 100 g of anhydrous sodium sulfate and 10 g of sodium carbonate to a 400-mL beaker, and add water to dissolve the two salts. Transfer the solution to a 1000-mL volumetric flask, dilute with water to volume, and mix.
Procedure— Dissolve about 50 mg of Docusate Sodium, accurately weighed, in 50 mL of chloroform in a glass-stoppered, 250-mL conical flask. Add 50 mL of Salt solution and 0.5 mL of bromophenol blue TS, and mix. Titrate with Tetra-n-butylammonium iodide solution until about 1 mL from the endpoint, and shake the stoppered flask vigorously for about 2 minutes. Continue the titration in 2-drop increments, shaking vigorously for about 10 seconds after each addition, and then allow the flask to stand about 10 seconds. Continue the titration until the chloroform layer just assumes a blue color. Each mL of Tetra-n-butylammonium iodide solution is equivalent to 3.009 mg of C20H37NaO7S.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Elena Gonikberg, Ph.D.
Senior Scientist
(MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
Reference Standards Lili Wang, Technical Services Scientist
USP32–NF27 Page 2195
Pharmacopeial Forum: Volume No. 31(3) Page 753
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.