Phenytoin Sodium Injection

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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1 DEFINITION

Phenytoin Sodium Injection is a sterile solution of Phenytoin Sodium with Propylene Glycol and Alcohol in Water for Injection. It contains NLT

95.0% and NMT 105.0% of the labeled amount of phenytoin sodium (C₁₅H₁₁N₂NaO₂).

2 IDENTIFICATION

Change to read:

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

Sample: Transfer an equivalent of 250 mg of phenytoin sodium from a volume of Injection to a separator containing 25 mL of water. Extract first with 50 mL of ethyl acetate and then with two additional 30-mL portions of ethyl acetate. Wash each extract with two 20-mL portions of sodium acetate solution (10 mg/mL). Evaporate the combined ethyl acetate extracts, and dry the residue of phenytoin at 105° to constant weight.

Acceptance criteria: Residue obtained from the Sample meets the requirements.

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

3 ASSAY

Procedure

Mobile phase: Methanol and water (55:45)

Standard solution: 0.23 mg/mL of USP Phenytoin RS in Mobile phase

Sample solution: Nominally 0.25 mg/mL of phenytoin sodium from a volume of Injection equivalent to 250 mg of phenytoin sodium in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 25-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of phenytoin sodium (C₁₅H₁₁N₂NaO₂) in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = nominal concentration of phenytoin sodium in the Sample solution (mg/mL)

M_r1 = molecular weight of phenytoin sodium, 274.25

M_r2 = molecular weight of phenytoin, 252.27

Acceptance criteria: 95.0%–105.0%

4 OTHER COMPONENTS

Alcohol and Propylene Glycol Content

Internal standard solution: 0.02 mL/mL of methanol and 0.04 mL/mL of ethylene glycol in water

Standard stock solution: 0.01 mL/mL of alcohol from USP Alcohol Determination–Alcohol RS and 0.04 mL/mL of USP Propylene Glycol RS in water

Standard solution: 0.005 mL/mL of alcohol and 0.02 mL/mL of propylene glycol prepared as follows. Pipet 5 mL each of Standard stock solution and Internal standard solution into a 10-mL volumetric flask.

Sample solution: 0.05 mL/mL of Injection in water prepared as follows. Pipet 5 mL of Injection and 50 mL of the Internal standard solution into a 100-mL volumetric flask, and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 30-m × 0.53-mm (ID) capillary column with a 1-μm coating of G16 phase

Temperatures

Injection port: 240°

Detector: 250°

Column: See Table 1.

Table 1

Carrier gas: Hydrogen or helium

Flow rate: 5 mL/min

Injection volume: 0.2 μL

Injection type: Split ratio, 10:1

System suitability

Sample: Standard solution

[Note - See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 5.0 between methanol and alcohol; NLT 5.0 between propylene glycol and ethylene glycol

Relative standard deviation: NMT 2.0% for each of the response ratios of alcohol to methanol and propylene glycol to ethylene glycol

Analysis

Samples: Standard solution and Sample solution

Calculate the alcohol content, as a percentage, in the portion of Injection taken:

Result = (R_U/R_S) × (C_S/C_U) × 100

R_U = peak response ratio of alcohol to methanol from the Sample solution

R_S = peak response ratio of alcohol to methanol from the Standard solution

C_S = concentration of alcohol in the Standard solution (mL/mL)

C_U = nominal concentration of the Injection in the Sample solution (mL/mL)

Calculate the propylene glycol content, as a percentage, in the portion of Injection taken:

Result = (R_U/R_S) × (C_S/C_U) × 100

R_U = peak response ratio of propylene glycol to ethylene glycol from the Sample solution

R_S = peak response ratio of propylene glycol to ethylene glycol from the Standard solution

C_S = concentration of propylene glycol in the Standard solution (mL/mL)

C_U = nominal concentration of the Injection in the Sample solution (mL/mL)

Acceptance criteria: See Table 2.

Table 2

^aInternal standard included for peak identification purposes only.

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: It contains NMT 0.3 USP Endotoxin Unit/mg of phenytoin sodium.

pH 〈791〉: 10.0–12.3

Particulate Matter in Injections 〈788〉: It meets the requirements under small-volume injections.

Other Requirements: It meets the requirements under Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, at controlled room temperature.

Labeling: The label states the following: “Do not use the Injection if it is hazy or contains a precipitate.”

USP Reference Standards 〈11〉

USP Alcohol Determination–Alcohol RS

USP Phenytoin RS

USP Propylene Glycol RS