Mercaptopurine Tablets
»Mercaptopurine Tablets contain not less than 93.0percent and not more than 110.0percent of the labeled amount of mercaptopurine (C5H4N4S·H2O).
Packaging and storage— Preserve in well-closed containers.
Identification—
A: The UVabsorption spectrum of the solution of Tablets employed for measurement of absorbance in the Assayexhibits a maximum at 325±2nm,and the ratio A255/A325does not exceed 0.09.
B: Triturate a quantity of finely powdered Tablets,equivalent to about 600mg of mercaptopurine,with three 25-mLportions of hot alcohol.Filter the hot alcohol extracts,and evaporate the filtrate on a steam bath to dryness.Add to the residue 5mLof sodium hydroxide solution (1in 33),agitate well,and filter:the clear filtrate so obtained responds to Identificationtest Bunder Mercaptopurine.
Delete the following:
Disintegration á701ñ: 30minutes.USP28
Add the following:
Dissolution á711ñ—
Medium: 0.1Nhydrochloric acid;900mL.
Apparatus 2: 50rpm.
Time: 60minutes.
Determine the amount of C5H4N4Sdissolved by employing the following method.
Mobile phase— Prepare a filtered and degassed solution of 0.1%acetic acid in water.Make adjustments if necessary (see System Suitability under Chromatography á621ñ).
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 230-nm detector and a 3.9-mm ×15-cm column that contains packing L1.The flow rate is about 2.5mLper minute.Chromatograph replicate injections of the Standard solution prepared as described below for Procedure,and record the peak responses as directed for Procedure:the retention time for mercaptopurine is not less than 4minutes,and the relative standard deviation is not more than 2.0%.
Procedure— Inject a volume (about 10µL)of a filtered portion of the solution under test into the chromatograph,record the chromatogram,and measure the response for the major peak.Calculate the quantity of C5H4N4Sdissolved in comparison with a Standard solution having a known concentration of USP Mercaptopurine RSin the same Medium and similarly chromatographed.
Tolerances— Not less than 80%(Q)of the labeled amount of C5H4N4Sis dissolved in 60minutes.USP28
Uniformity of dosage units á905ñ: meet the requirements.
Assay— Weigh and finely powder not fewer than 20Tablets.Accurately weigh a portion of the powder,equivalent to about 50mg of mercaptopurine,and transfer to a 100-mLvolumetric flask.Add 20mLof water and 1.5mLof 1Nsodium hydroxide,and swirl for not more than 5minutes.Dilute with water to volume,mix,and filter,discarding the first 20mLof the filtrate.Dilute an accurately measured portion of the filtrate quantitatively and stepwise with 0.1Nhydrochloric acid to give a final concentration of about 5µg per mL.Dissolve an accurately weighed quantity of USP Mercaptopurine RSin a mixture of 10mLof water and 1mLof 1Nsodium hydroxide contained in a 100-mLvolumetric flask,dilute with water to volume,and mix.Dilute an aliquot of this solution quantitatively and stepwise with 0.1Nhydrochloric acid to obtain a Standard solution having a known concentration of about 5µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 325nm,with a suitable spectrophotometer,using 0.1Nhydrochloric acid as the blank.Calculate the quantity,in mg,of mercaptopurine (C5H4N4S·H2O)in the portion of Tablets taken by the formula:
(170.19/152.18)10C(AU/AS),
in which 170.19and 152.18are the molecular weights of mercaptopurine monohydrate and anhydrous mercaptopurine,respectively;Cis the concentration,in µg per mL,of USP Mercaptopurine RSin the Standard solution;and AUand ASare the absorbances of the solution from Tablets and the Standard solution,respectively.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 1216
Pharmacopeial Forum:Volume No.30(4)Page 1261
Phone Number:1-301-816-8389