Fosphenytoin Sodium Injection
» Fosphenytoin Sodium Injection is a sterile solution of Fosphenytoin Sodium in Water for Injection. Fosphenytoin Sodium is a prodrug. Injection containing 1 mg per mL of Fosphenytoin Sodium is equivalent to 0.667 mg per mL of Phenytoin Sodium after injection. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of fosphenytoin sodium (C16H13N2Na2O6P).
Packaging and storage Preserve in single-dose or multiple-dose containers, preferably of Type I glass. Store between 2 and 8. Do not store at room temperature for more than 48 hours.
Labeling Both the actual content of Fosphenytoin Sodium and the content of Phenytoin Sodium, expressed in terms of phenytoin sodium equivalents, are stated prominently on the label.
USP Reference standards 11
A: Infrared Absorption 197K
Test specimen Transfer a 5-mL aliquot of Injection to a 100-mL beaker, add 30 mL of acetone to form a white precipitate, and stir for 20 minutes using a magnetic stirrer. Filter in vacuum, and collect the precipitate using suitable filter paper. Allow to dry in vacuum for 15 minutes.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Bacterial endotoxins 85: not more than 14 USP Endotoxin Units per mL.
pH 791: between 8.3 and 9.3.
Buffer solution, Mobile phase, Standard stock solution 1, Standard stock solution 2, and Chromatographic system Proceed as directed in the Assay.
Standard solution Use the Standard preparation, prepared as directed in the Assay.
Test solution Use the Assay preparation, prepared as directed in the Assay.
Procedure Inject a volume (about 40 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak areas. Calculate the percentages of phenytoin, phenytoin related compound A, phenytoin related compound B, and unknown impurities in each mL of Injection taken by the formula:
200,000(C/VL)(ri / rS)in which C is the concentration, in mg per mL, of the respective impurity in the Standard solution; V is the volume, in mL, of the Injection taken to prepare the Test solution; L is the labeled amount, in mg per mL, of fosphenytoin sodium in the Injection; and ri and rS are the individual peak responses of the impurities in the chromatograms obtained from the Test solution and the Standard solution, respectively: not more than 1.5% of phenytoin related compound B is found; not more than 0.2% of phenytoin is found; not more than 0.2% of phenytoin related compound A is found; not more than 0.1% of any individual unknown impurity is found; and not more than 2.0% total impurities is found. [noteUse the peak area and concentration of the USP Phenytoin RS in the Standard solution as rS and C, respectively, to calculate the percentage of the unknown impurities. ]
Other requirements It meets the requirements under Injections 1.
Buffer solution Dissolve about 8.2 g of monobasic potassium phosphate in 1 L of water. Adjust with 6 N potassium hydroxide solution to a pH of 6.5 ± 0.05.
Mobile phase Prepare a filtered and degassed mixture of Buffer solution, methanol, and acetonitrile (73:25:2). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard stock solution 1 Dissolve an accurately weighed quantity of USP Fosphenytoin Sodium RS in methanol, and dilute quantitatively, and stepwise if necessary, with Buffer solution to obtain a solution having a known concentration of about 0.75 mg per mL.
Standard stock solution 2 Dissolve an accurately weighed quantity of USP Phenytoin RS, USP Phenytoin Related Compound A RS, and USP Phenytoin Related Compound B RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 0.0075 mg per mL, 0.0075 mg per mL, and 0.015 mg per mL, respectively.
Standard preparation Transfer 10.0 mL of Standard stock solution 1 and 5.0 mL of Standard stock solution 2 to a 50-mL volumetric flask. Dilute with Buffer solution to volume, and mix.
Assay preparation Transfer an accurately measured volume of the Injection, equivalent to about 300 mg of fosphenytoin, to a 200-mL volumetric flask, dilute with methanol to volume, and mix. Transfer 5.0 mL of this solution to a 50-mL volumetric flask. Dilute with Buffer solution to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm × 15-cm column that contains packing L11. The flow rate is about 1.25 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.3 for phenytoin related compound B, about 0.5 for phenytoin related compound A, 1.0 for fosphenytoin, and about 3.8 for phenytoin; the resolution, R, between phenytoin related compound B and phenytoin related compound A is not less than 4.0; the column efficiency is not less than 2250 theoretical plates for the fosphenytoin peak; the tailing factor is not more than 1.8 for the fosphenytoin peak; and the relative standard deviation for replicate injections is not more than 1.0% for the fosphenytoin peak and not more than 5.0% for the phenytoin related compound B, phenytoin related compound A, and phenytoin peaks.
Procedure Separately inject equal volumes (about 40 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak areas for fosphenytoin. Calculate the quantity, in mg, of fosphenytoin sodium (C16H13N2Na2O6P) in each mL of the Injection taken by the formula:
2000(C/V)(rU / rS)in which C is the concentration, in mg per mL, of USP Fosphenytoin Sodium RS in the Standard preparation; V is the volume, in mL, of the Injection taken to prepare the Assay preparation; and rU and rS are the fosphenytoin peak areas obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3286Pharmacopeial Forum: Volume No. 29(5) Page 1493