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Probenecid
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C13H19NO4S 285.36

Benzoic acid, 4-[(dipropylamino)sulfonyl]-.
p-(Dipropylsulfamoyl)benzoic acid [57-66-9].
» Probenecid contains not less than 98.0 percent and not more than 101.0 percent of C13H19NO4S, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification—
B: Ultraviolet Absorption 197U—
Solution: 20 µg per mL.
Medium: alcohol.
Absorptivities at 248 nm, calculated on the dried basis, do not differ by more than 3.0%.
Melting range 741: between 198 and 200.
Acidity— To 2.0 g add 100 mL of water, heat on a steam bath for 30 minutes, cool, filter, and dilute with water to 100.0 mL. To 25.0 mL of this solution add 1 drop of phenolphthalein TS, and titrate with 0.10 N sodium hydroxide: not more than 0.50 mL is required to produce a pink color.
Loss on drying 731— Dry it at 105 for 4 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Selenium 291: not more than 0.003%, a 100-mg test specimen, mixed with 100 mg of magnesium oxide, being used.
Heavy metals, Method II 231: not more than 0.002%.
Chromatographic purity—
Mobile phase , Assay preparation, and Chromatographic system—Proceed as directed in the Assay.
Test preparation— Use the Assay preparation.
Procedure— Inject about 20 µL of the Test preparation into the chromatograph, record the chromatograms, and measure the responses for all of the peaks. Calculate the percentages of each peak, other than the solvent peak and the probenecid peak, in the portion of Probenecid taken by the formula:
100(rI / rT),
in which rI is the response of each peak and rT is the sum of the responses of all of the peaks, excluding that of the solvent peak: not more than 0.5% of any individual impurity and not more than 2.0% of total impurities is found.
Organic volatile impurities, Method V 467: meets the requirements.
Solvent— Use dimethyl sulfoxide.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Sodium phosphate solution— Prepare in glacial acetic acid solution (1 in 100) a 0.05 M solution of monobasic sodium phosphate, and adjust with phosphoric acid to a pH of 3.0.
Mobile phase— Prepare a degassed and filtered mixture (50:50) of Sodium phosphate solution and a 1 in 100 solution of glacial acetic acid in acetonitrile. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Probenecid RS in Mobile phase to obtain a solution having a known concentration of about 0.50 mg per mL.
Assay preparation— Transfer about 50 mg of Probenecid, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L11. 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 2.3, the number of theoretical plates is not less than 3900, 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 C13H19NO4S in the portion of Probenecid taken by the formula:
100C(rU / rS),
in which C is the concentration, in mg per mL, of USP Probenecid RS in the Standard preparation, and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Elena Gonikberg, Ph.D., Scientist
Expert Committee : (MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
USP29–NF24 Page 1801
Phone Number : 1-301-816-8251