Phenylbutazone
;)
3,5-Pyrazolidinedione,4-butyl-1,2-diphenyl-.
4-Butyl-1,2-diphenyl-3,5-pyrazolidinedione [50-33-9].
»Phenylbutazone contains not less than 98.0percent and not more than 102.0percent of C19H20N2O2,calculated on the dried basis.
Packaging and storage—
Preserve in tight containers.
Identification—
A:
Infrared Absorption á197Kñ.
B:
Ultraviolet Absorption á197Uñ—
Solution:
10µg per mL.
Medium:
sodium hydroxide solution (1in 2500).
Absorptivities at 264nm,calculated on the dried basis,do not differ by more than 2.0%.
Loss on drying á731ñ—
Dry it in vacuum at a pressure of 30±10mm of mercury at 80
for 4hours:it loses not more than 0.5%of its weight.
for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%,2.0g being used for the test.
Chloride á221ñ—
Boil 2.0g with 60mLof water for 5minutes,cool,and filter.To a 30-mLportion of the filtrate add 1mLof 2Nnitric acid and 1mLof silver nitrate TS:the filtrate shows no more chloride than corresponds to 0.10mLof 0.020Nhydrochloric acid (0.007%).
Sulfate á221ñ—
To a 30-mLportion of the filtrate obtained in the test for Chlorideadd 2mLof barium chloride TS:the mixture shows no more sulfate than corresponds to 0.10mLof 0.020Nsulfuric acid (0.01%).
Heavy metals,Method IIá231ñ:
0.001%.
Organic volatile impurities,Method Vá467ñ:
meets the requirements.
Solvent—
Use dimethyl sulfoxide.
Assay—
Acetate buffer—
Transfer 2.72g of sodium acetate to a 1000-mLbeaker,and dissolve in about 700mLof water.Adjust with glacial acetic acid to a pHof 4.1.Filter through a 0.5-µm filter,dilute with filtered water to 1000mL,and mix.
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile with 560mLof Acetate buffer(440:560).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Internal standard solution—
Dissolve 300mg of desoxycorticosterone acetate in 200mLof acetonitrile,and mix.
Standard preparation—
Dissolve an accurately weighed quantity of USP Phenylbutazone RSin acetonitrile,with the aid of sonication,and dilute quantitatively with acetonitrile to obtain a solution having a concentration of about 1.4mg per mL.Pipet 10mLof this solution into a 50-mLvolumetric flask,add 10.0mLof Internal standard solution,dilute with acetonitrile to volume,and mix.[NOTE—Use this solution within 8hours of its preparation.]
Assay preparation—
Transfer about 140mg of Phenylbutazone,accurately weighed,to a 100-mLvolumetric flask,add 75mLof acetonitrile,and sonicate to dissolve.Dilute with acetonitrile to volume,and mix.Pipet 10mLof this solution into a 50-mLvolumetric flask,add 10.0mLof Internal standard solution,dilute with acetonitrile to volume,and mix.[NOTE—Use this solution within 8hours of its preparation.]
Chromatographic system(see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×25-cm column that contains packing L7,preceded by a pre-column that contains packing L2.The flow rate is about 2.4mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,of phenylbutazone and the internal standard is not less than 3.5,and the relative standard deviation of the ratio of their peak responses in replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 25µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 1.0for the internal standard and 0.7for phenylbutazone.Calculate the quantity,in mg,of C19H20N2O2in the portion of Phenylbutazone taken by the formula:
500C(RU/RS),
in which Cis the concentration,in mg per mL,of USP Phenylbutazone RSin the Standard preparation;and RUand RSare the ratios of the peak response of the phenylbutazone to that of the internal standard for the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 1539
Pharmacopeial Forum:Volume No.28(5)Page 1440
Phone Number:1-301-816-8143