Sodium Phenylbutyrate Oral Powder

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

Sodium Phenylbutyrate Oral Powder contains NLT 90.0% and NMT 110.0% of the labeled amount of sodium phenylbutyrate (C₁₀H₁₁NaO₂ ).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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, water, and glacial acetic acid (49:50:1)

Diluent: Methanol and water (20:80)

Standard solution: 2.5 mg/mL of USP Sodium Phenylbutyrate RS in Diluent. Sonicate, if necessary, to dissolve.

Sample solution: Nominally 2.5 mg/mL of sodium phenylbutyrate in Diluent prepared as follows. Transfer an amount of Oral Powder equivalent to about 500 mg of sodium phenylbutyrate to a 200-mL volumetric flask. Add about 140 mL of Diluent, and sonicate for 10 min with intermittent shaking. Dilute with Diluent to volume. Pass through a suitable fIlter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm. For Identi

cation A, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1.2 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 sodium phenylbutyrate (C₁₀H₁₁NaO₂ ) in the portion of Oral Powder 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 Sodium Phenylbutyrate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Simulated intestinal

uid without enzyme; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Mobile phase: Methanol, water, and glacial acetic acid (49:50:1)

Standard solution: (L/900) mg/mL of USP Sodium Phenylbutyrate RS, where L is the label claim of sodium phenylbutyrate in milligrams for each dosage strength prepared as follows. Transfer the appropriate amount of USP Sodium Phenylbutyrate RS to a volumetric flask. Add 40% of the final volume of methanol, and sonicate, if necessary, to dissolve. Dilute with Medium to volume.

Sample solution: Transfer carefully an amount of Oral Powder equivalent to each dosage strength, based on the label claim, to the dissolution vessel containing the Medium. Perform the dissolution test and pass a portion of the solution under test through a suitable fIlter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 245 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1.7 mL/min

Injection volume: 10 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 sodium phenylbutyrate (C₁₀H₁₁NaO₂ ) dissolved:

Result = (r_U /r_S ) × (C_S /L) × V × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

L = label claim (mg/dosage strength)

V = volume of Medium, 900 mL

Tolerances: NLT 85% (Q) of the labeled amount of sodium phenylbutyrate (C₁₀H₁₁NaO₂ ) is dissolved.

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

Organic Impurities

Mobile phase: Methanol, water, and glacial acetic acid (44:55:1)

Diluent: Methanol and water (20:80)

System suitability stock solution A: 0.08 mg/mL of USP Phenylbutyrate Related Compound A RS in Diluent. Sonicate to dissolve, if necessary.

System suitability stock solution B: 0.06 mg/mL of USP Phenylbutyrate Related Compound B RS in Diluent. Sonicate to dissolve, if necessary.

System suitability solution: 4 mg/mL of USP Sodium Phenylbutyrate RS, 0.008 mg/mL of USP Phenylbutyrate Related Compound A RS, and

0.006 mg/mL of USP Phenylbutyrate Related Compound B RS prepared as follows. Dissolve a suitable amount of USP Sodium

Phenylbutyrate RS with 50% of the total flask volume of methanol and sonicate, if necessary, to dissolve. Add suitable volumes of System suitability stock solution A and System suitability stock solution B to the same flask and dilute with Diluent to volume.

Sensitivity solution: 1.5 μg/mL each of USP Phenylbutyrate Related Compound A RS and USP Phenylbutyrate Related Compound B RS from

System suitability stock solution A and System suitability stock solution B in Diluent

Standard solution: 0.008 mg/mL of USP Phenylbutyrate Related Compound A RS and 0.006 mg/mL of USP Phenylbutyrate Related

Compound B RS from System suitability stock solution A and System suitability stock solution B in Diluent

Sample solution: Nominally 4 mg/mL of sodium phenylbutyrate in Diluent prepared as follows. Transfer an amount of Oral Powder equivalent to about 200 mg of sodium phenylbutyrate to a 50-mL volumetric flask. Add about 35 mL of Diluent and sonicate for 10 min with intermittent shaking. Dilute with Diluent to volume. Pass through a suitable fIlter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 245 nm

Column: 2.1-mm × 10-cm; 1.7-μm packing L1

Column temperature: 35°

Flow rate: 0.2 mL/min

Injection volume: 2 μL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

Suitability requirements

Resolution: NLT 6.0 between the phenylbutyrate related compound B and phenylbutyrate peaks, System suitability solution

Relative standard deviation: NMT 5.0% for the phenylbutyrate related compound A and phenylbutyrate related compound B peaks, Standard solution

Signal-to-noise ratio: NLT 10 for the phenylbutyrate related compound A and phenylbutyrate related compound B peaks, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phenylbutyrate related compound A or phenylbutyrate related compound B in the portion of Oral Powder taken:

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

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

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

C_S = concentration of USP Phenylbutyrate Related Compound A RS or USP Phenylbutyrate Related Compound B RS in the Standard solution (mg/mL)

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

Calculate the percentage of any individual unspecified impurity in the portion of Oral Powder taken:

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

r_U = peak response of any individual unspecified impurity from the Sample solution

r_S = peak response of phenylbutyrate related compound A from the Standard solution

C_S = concentration of USP Phenylbutyrate Related Compound A RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 10² cfu/g. The total molds and yeasts count does not exceed 10 cfu/g. It meets the requirements of the test for absence of Escherichia coli.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Sodium Phenylbutyrate RS

USP Phenylbutyrate Related Compound A RS

3-Benzoylpropionic acid;

4-Oxo-4-phenylbutanoic acid.

C₁₀H₁₀O₃  178.18

USP Phenylbutyrate Related Compound B RS

α-Tetralone;

3,4-Dihydronaphthalen-1(2H)-one.

C₁₀H₁₀O 146.19 (USP 1-May-2021)