Fosphenytoin Sodium

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₆H₁₃N₂Na₂O₆P 406.24

2,4-Imidazolidinedione, 5,5-diphenyl-3- [(phosphonooxy)methyl]-, disodium salt;

3-(Hydroxymethyl)-5,5-diphenylhydantoin, disodium phosphate (ester) CAS RN®: 92134-98-0; UNII: 7VLR55452Z.

1 DEFINITION

Fosphenytoin Sodium contains NLT 98.0% and NMT 102.0% of fosphenytoin sodium (C₁₆H₁₃N₂Na₂O₆P), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. Identification Tests - General, Sodium〈191〉: Meets the requirements

3 ASSAY

3.1 Procedure

Buffer: Dissolve 6.80 g of monobasic potassium phosphate and 30 mL of 0.5 M dodecyltriethylammonium phosphate in 900 mL of water. Adjust with 1.5 M phosphoric acid to a pH of 5.0, and dilute with water to 1000 mL.

Mobile phase: Acetonitrile and Buffer (35:65)

Standard solution: 0.15 mg/mL of USP Fosphenytoin Sodium RS in Mobile phase

Sample solution: 0.15 mg/mL of Fosphenytoin Sodium in Mobile phase

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 3.9-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Column efficiency: NLT 5000 theoretical plates

Tailing factor: NMT 1.6

Relative standard deviation: NMT 0.5%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fosphenytoin sodium (C₁₆H₁₃N₂Na₂O₆P) in the portion of Fosphenytoin Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fosphenytoin Sodium RS in the Standard solution (mg/mL)

C_U = concentration of Fosphenytoin Sodium in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

4.1 Organic Impurities

Buffer and Mobile phase: Proceed as directed in the Assay.

Standard solution: 0.003 mg/mL of USP Phenytoin Related Compound A RS, 0.003 mg/mL of USP Phenytoin Related Compound B RS, and 0.0015 mg/mL of USP Phenytoin RS in Mobile phase

Sample solution: 3 mg/mL of Fosphenytoin Sodium in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except use a run time of NLT 6 times the retention time of the major peak.

4.2 System suitability

Sample: Standard solution

[Note - The order of elution is phenytoin related compound A, phenytoin, phenytoin related compound B, followed by the major peak due to fosphenytoin.]

4.3 Suitability requirements

Resolution: NLT 2.0 between phenytoin and phenytoin related compound B

Relative standard deviation: NMT 5.0% for each compound

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phenytoin, phenytoin related compound A, and phenytoin related compound B, if present, in the portion of Fosphenytoin Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of phenytoin, phenytoin related compound A, or phenytoin related compound B from the Sample solution

r_S= peak response of phenytoin, phenytoin related compound A, or phenytoin related compound B from the Standard solution

C_S = concentration of the corresponding analyte in the Standard solution (mg/mL)

C_U = concentration of Fosphenytoin Sodium in the Sample solution (mg/mL)

Calculate the percentage of any unspecified individual impurity in the portion of Fosphenytoin Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each unspecified impurity from the Sample solution

r_S = peak response of phenytoin from the Standard solution

C_S = concentration of the USP Phenytoin RS in the Standard solution (mg/mL)

C_U = concentration of Fosphenytoin Sodium in the Sample solution (mg/mL)

Acceptance criteria

Phenytoin: NMT 0.1%

Any other impurity: NMT 0.1%

Total impurities: NMT 0.5%

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 75 mg/mL of Fosphenytoin Sodium in water

Acceptance criteria: 8.5–9.5

Water Determination, Method I 〈921〉: 21.7%–25.7%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Fosphenytoin Sodium RS

USP Phenytoin RS

USP Phenytoin Related Compound A RS

Diphenylglycine.

C₁₄H₁₃NO₂ 227.26

USP Phenytoin Related Compound B RS

Diphenylhydantoic acid.

C₁₅H₁₄N₂O₃ 270.29