U.S. PHARMACOPEIA

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Amifostine for Injection
» Amifostine for Injection is a sterile, lyophilized crystalline substance suitable for parenteral use. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of amifostine (C5H15 N2O3PS).
Packaging and storage— Preserve in tight Containers for Sterile Solids as described under Injections 1, and store at controlled room temperature.
Constituted solution— At the time of use, it meets the requirements for Constituted Solutions under Injections 1. When constituted with 0.9% Sodium Chloride Injection, the solution must completely dissolve in 45 seconds.
Bacterial endotoxins 85 It contains not more than 0.2 USP Endotoxin Unit per mg of amifostine.
Sterility 71 It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
pH 791: between 6.5 and 7.5, in a solution constituted as directed in the labeling.
Water, Method Ic 921: between 18.0% and 22.0%, when tested as directed in the test for Water under Amifostine.
Particulate matter 788: meets the requirements for small-volume injections.
Related compounds—
Mobile phase, Blank solution, and Test solution— Prepare as directed in the test for Related compounds under Amifostine.
Standard thiol solution— Transfer about 40.1 mg of USP Amifostine Thiol RS, accurately weighed, to a 50-mL volumetric flask. Dissolve in and dilute with water to volume, and mix. [NOTE—Inject immediately after preparation, or refrigerate until use. The solution is stable for 48 hours if maintained at about 5.]
Standard disulfide solution— Transfer about 18.6 mg of USP Amifostine Disulfide RS, accurately weighed, to a 100-mL volumetric flask. Dissolve in and dilute with water to volume, and mix. [NOTE—Inject immediately after preparation, or refrigerate until use. The solution is stable for 48 hours if maintained at about 5.]
System suitability solution— Dissolve about 5.0 mg of USP Amifostine RS, accurately weighed, in 1 mL of Standard thiol solution, and mix. [NOTE—Inject immediately after preparation, or refrigerate until use. The solution is stable for 12 hours if maintained at about 5.]
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a detector capable of recording at both 220 nm and 247 nm, and a 4.6-mm × 25-cm column that contains packing L1. The column temperature is maintained at 30, and the temperature of solutions to be injected is maintained at between 2 and 8. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability solution, the Standard disulfide solution, and the Standard thiol solution, and record the peak responses as directed for Procedure: the column efficiency calculated for the amifostine thiol peak is not less than 2300 theoretical plates; the tailing factor is not more than 4.0; the capacity factor, k¢, is more than 0.5; and the relative standard deviation for replicate injections is not more than 4.0%. The column efficiency calculated for the amifostine disulfide peak is not less than 2000 theoretical plates; the tailing factor is not more than 4.5; the capacity factor, k¢, is more than 2.2; and the relative standard deviation for replicate injections is not more than 4.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard thiol solution, the Standard disulfide solution, the Test solution, and the Blank solution into the chromatograph, record the chromatograms, and measure the responses of all the peaks except the peaks corresponding to those obtained from the Blank solution. Calculate the percentage of amifostine thiol in the portion of Amifostine for Injection taken by the formula:
(134.24/207.17)1000(C/W)(rU / rS),
in which 134.24 and 207.17 are the molecular weights of amifostine thiol and amifostine thiol dihydrochloride, respectively; C is the concentration, in mg per mL, of amifostine thiol dihydrochloride in the Standard thiol solution; W is the weight, in mg, of amifostine taken to prepare the Test solution; and rU and rS are the amifostine thiol peak responses recorded at 220 nm, obtained from the Test solution and the Standard thiol solution, respectively. Calculate the percentage of amifostine disulfide in the portion of Amifostine for Injection taken by the formula:
(266.47/412.31)(10C)(rU / rS),
in which 266.47 and 412.31 are the molecular weights of amifostine disulfide and amifostine disulfide tetrahydrochloride, respectively; C is the concentration, in mg per mL, of USP Amifostine Disulfide RS in the Standard disulfide solution; and rU and rS are the peak responses recorded at 247 nm, obtained from the Test solution and the Standard disulfide solution, respectively: not more than 2.0% of total impurities, including amifostine thiol and amifostine disulfide, is found. Calculate the percentage of each of the other impurities in the portion of Amifostine for Injection taken by the formula:
100(ri / rA),
in which ri and rA are the peak responses for each impurity and amifostine, respectively, obtained from the Test solution: not more than 0.1% of any individual impurity except amifostine thiol is found.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Other requirements— It meets the requirements under Uniformity of Dosage Units 905 and for Labeling under Injections 1. It also meets the requirements of the tests for Identification and X-ray diffraction under Amifostine.
Assay—
Mobile phase, Standard preparation, and Chromatographic system— Prepare as directed in the Assay under Amifostine.
Assay preparation— Transfer an accurately weighed quantity of Amifostine for Injection, equivalent to about 500 mg of amifostine, to a 50-mL volumetric flask, dissolve in 10 mL of water, dilute with water to volume, and mix. Transfer 6.0 mL of this solution to a 25-mL volumetric flask, add 6.5 mL of water, dilute with methanol to volume, and mix.
Procedure— Proceed as directed in the Assay under Amifostine. Calculate the quantity, in mg, of amifostine (C5H15N2O3PS) in the portion of Amifostine for Injection taken by the formula:
208.33C(rU / rS),
in which C is the concentration, in mg per mL, of USP Amifostine 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 : Andrzej Wilk, Ph.D., Senior Scientific Associate
Expert Committee : (MDCV05) Monograph Development-Cardiovascular
USP29–NF24 Page 126
Pharmacopeial Forum : Volume No. 30(6) Page 1976
Phone Number : 1-301-816-8305