Mercaptopurine
;)
6H-Purine-6-thione,1,7-dihydro-,monohydrate.
Purine-6-thiol monohydrate [6112-76-1].
Anhydrous 152.18 [50-44-2].
»Mercaptopurine contains not less than 97.0percent and not more than 102.0percent of C5H4N4S,calculated on the anhydrous basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:
Ultraviolet Absorption á197Uñ—
Solution:
5µg per mL.
Medium:
0.1Nhydrochloric acid.
Absorptivities at 325nm,calculated on the anhydrous basis,do not differ by more than 3.0%.The ratio A255/A325does not exceed 0.06.
B:
To a solution of 600mg in 6mLof sodium hydroxide solution (1in 33)add slowly,with shaking,0.5mLof methyl iodide.Allow the mixture to stand for 2hours at room temperature,cool in an ice bath,and adjust with acetic acid to a pHof about 5.Collect the crystals,and recrystallize from hot water:the methylmercaptopurine trihydrate so obtained,dried at 120
for 30minutes,melts between 218and 222,with decomposition.
for 30minutes,melts between 218and 222,with decomposition.
Water,Method Iá921ñ:
not more than 12.0%.
Phosphorus—
Digest 200mg with 2mLof 15Nsulfuric acid in a large test tube,periodically adding nitric acid,dropwise and with caution.Continue heating until practically all of the liquid has evaporated and the residue is colorless.Transfer the residue,with the aid of small portions of water,to a 25-mLvolumetric flask,add 1mLof 15Nsulfuric acid,0.5mLof nitric acid,0.75mLof ammonium molybdate TS,and 1mLof aminonaphtholsulfonic acid TS,then dilute with water to volume,and mix.Allow to stand for 5minutes,and determine the absorbance of this solution at 750nm,with a suitable spectrophotometer,using as a blank a solution of the same quantities of the same reagents,prepared in the same manner.The absorbance of this solution is not greater than that of a solution obtained by treating as directed above,beginning with “add 1mLof 15Nsulfuric acid,”a 2-mLportion of a standard phosphate solution prepared to contain,in each mL,43.96µg of dried monobasic potassium phosphate,equivalent to 10µg of P(0.010%).
Organic volatile impurities,Method Vá467ñ:
meets the requirements.
Solvent—
Use dimethyl sulfoxide.
Assay—
Dissolve about 300mg of Mercaptopurine,accurately weighed,in 80mLof dimethylformamide.Add 5drops of a 1in 100solution of thymol blue in dimethylformamide,and titrate with 0.1Nsodium methoxide VS,using a magnetic stirrer and taking precautions against absorption of atmospheric carbon dioxide.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nsodium methoxide is equivalent to 15.22mg of C5H4N4S.
Auxiliary Information—
Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 1216
Phone Number:1-301-816-8389