Butabarbital Sodium Oral Solution

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

Butabarbital Sodium Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of butabarbital sodium (C₁₀H₁₅N₂NaO₃).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

Sample: Transfer an equivalent to 150 mg of butabarbital sodium from a volume of Oral Solution, to a separator. Render it distinctly alkaline by the addition of 1 N sodium hydroxide, and saturate it with sodium chloride. Extract the mixture with two 15-mL portions of ether, and discard the ether. Acidify the solution with hydrochloric acid, and render it just alkaline to litmus by adding small portions of sodium bicarbonate (carbonate-free). Extract the liberated acid barbiturate using five 20-mL portions of chloroform. Wash the combined chloroform extracts with 10 mL of water acidified with 1 drop of hydrochloric acid, then extract the water with 10 mL of chloroform, adding the latter to the main chloroform solution. Pass the chloroform solution through a pledget of cotton or other suitable filter, previously washed with chloroform, into a tared beaker, and finally wash the separator and the filter with three 5-mL portions of chloroform. Evaporate the combined chloroform solution and washings on a steam bath with the aid of a current of air to dryness, and dry the residue at 105° for 2 h.

Acceptance criteria: Meets the requirements

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

3 ASSAY

3.1 PROCEDURE

Solution A: Dissolve 2.0 mL of bromine and 10 g of potassium bromide in 60 mL of water.

Solution B: Sodium metabisulfite in water (1 in 10)

Internal standard solution: 0.7 mg/mL of secobarbital in chloroform

Standard solution: 1 mg/mL of USP Butabarbital RS and 1.4 mg/mL of secobarbital in chloroform

Sample stock solution: Nominally 0.3 mg/mL of butabarbital sodium from Oral Solution prepared as follows. Transfer a volume of Oral Solution, equivalent to 30 mg of butabarbital sodium, to a separator. Add 1 mL of Solution A, and swirl. Allow to stand for 5 min, add 1 mL of Solution B, and swirl. Add 300 mg of sodium bicarbonate in small portions, with mixing, and extract with four 10-mL portions of chloroform. Pass the extracts through about 15 g of anhydrous sodium sulfate that is supported on a funnel by a small pledget of glass wool. Collect the combined filtrates in a 50-mL volumetric flask, wash the sodium sulfate with 5 mL of chloroform, collecting the washing with the filtrate, dilute with chloroform to volume, and mix.

[NOTE-This solution includes a bromination step for elimination of parabens and a carbonate-chloroform extraction for elimination of benzoic acid.]

Sample solution: Combine 2.0 mL of Sample stock solution with 2.0 mL of Internal standard solution in a suitable container, and reduce the volume to about 1 mL by evaporation, with the aid of a stream of dry nitrogen, at room temperature.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 4 - mm * 0.9 - m glass; packed with 3% liquid phase G10 support on 80- to 10-mesh S1A

Temperatures

Injection port:

225°

Detector: 225°

Column: 200 ± 10°

Carrier gas: A suitable gas such as dry nitrogen

Flow rate: 60-80 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for butabarbital and secobarbital are 0.6 and 1.0, respectively.]

Resolution: NLT 2.4 between butabarbital and secobarbital

Tailing factor: NMT 2.0 each for butabarbital and secobarbital

Relative standard deviation: NMT 1.5% for the peak response ratio of butabarbital to the internal standard

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of butabarbital sodium (C₁₀H₁₅N₂NaO₃) in the portion of Oral Solution taken:

Result = (R_U/R_S) × (C_S/C_U) x (M_r1/M_r2) × 100

R_U = peak response ratio of butabarbital to the internal standard from the Sample solution

R_S = peak response ratio of butabarbital to the internal standard from the Standard solution

C_S = concentration of USP Butabarbital RS in the Standard solution (µg/mL)

C_U = nominal concentration of butabarbital sodium in the Sample solution (µg/mL)

M_r1 = molecular weight of butabarbital sodium, 234.23

M_r2 = molecular weight of butabarbital, 212.25

Acceptance criteria: 90.0%-110.0%

4 OTHER COMPONENTS

ALCOHOL DETERMINATION, Method II(611): Between 95.0% and 115.0% of the labeled amount of alcohol (C₂H₅OH)

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Butabarbital RS