Butalbital

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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C₁₁H₁₆N₂O₃ 224.26

2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-(2-methylpropyl)-5-(2-propenyl)-;

5-Allyl-5-isobutylbarbituric acid  CAS RN^®: 77-26-9; UNII: KHS0AZ4JVK.

1 DEFINITION

Butalbital contains NLT 98.0% and NMT 102.0% of butalbital (C₁₁H₁₆N₂O₃), calculated on the dried 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.

3 ASSAY

PROCEDURE

Buffer: 1.0 mL of phosphoric acid diluted with water to 1 L

Mobile phase: Acetonitrile and Buffer (25:75)

System suitability solution: 0.1 mg/mL each of USP Butalbital RS and USP Salicylic Acid RS in Mobile phase. Sonication may be used to aid in dissolution.

Standard solution: 0.1 mg/mL of USP Butalbital RS in Mobile phase. Sonication may be used to aid in dissolution.

Sample solution: 0.1 mg/mL of Butalbital in Mobile phase. Sonication may be used to aid in dissolution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 10-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times of salicylic acid and butalbital are 0.86 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between salicylic acid and butalbital, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of butalbital (C₁₁H₁₆N₂O₃) in the portion of Butalbital 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 Butalbital RS in the Standard solution (mg/mL)

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

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

4.2 ORGANIC IMPURITIES

Buffer: 4.1 g/L of monobasic potassium phosphate adjusted with 1 N sodium hydroxide to a pH of 6.0

Mobile phase: Acetonitrile and Buffer (22:78)

System suitability solution: 10 µg/mL each of USP Butalbital RS and USP Butabarbital RS in Mobile phase. Sonication may be used to aid in dissolution.

Sample solution: 1 mg/mL of Butalbital in Mobile phase. Sonication may be used to aid in dissolution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 15-cm; 5-µm packing L78

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: System suitability solution

[Note—The relative retention times of butabarbital and butalbital are 0.83 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between butabarbital and butalbital

Tailing factor: NMT 1.5 for butalbital

Relative standard deviation: NMT 5.0% for butalbital

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Butalbital taken:

Result = (r_U/r_T) × 100

r_U = peak response of each impurity from the Sample solution

r_T = sum of the peak responses from the Sample solution

Acceptance criteria

Any individual unspecified impurity: NMT 0.10%

Total impurities: NMT 1%

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry under vacuum at room temperature to constant weight.

Acceptance criteria: NMT 0.2%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Butabarbital RS

USP Butalbital RS

USP Salicylic Acid RS