Pentobarbital

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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C₁₁H₁₈N₂O₃             226.28 (USP 1-Aug-2024)

2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-ethyl-5-(1-methylbutyl)-, (±)-;

(±)-5-Ethyl-5-(1-methylbutyl)barbituric acid;

(RS)-5-Ethyl-5-(pentan-2-yl)pyrimidine-2,4,6(1H,3H,5H)-trione (USP 1-Aug-2024) CAS RN®: 76-74-4; UNII: I4744080IR.

1 DEFINITION

Pentobarbital contains NLT 98.0% and NMT 102.0% of pentobarbital (C₁₁H₁₈N₂O₃), calculated on the dried basis. Where the material is labeled as intended solely for veterinary use, Pentobarbital contains NLT 97.0% and NMT 102.0% of pentobarbital (C₁₁H₁₈N₂O₃), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A (USP 1-Aug-2024)

(USP 1-Aug-2024)

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

Change to read:

Procedure

Mobile phase: Acetonitrile and 0.01 M monobasic potassium phosphate (35:65). Adjust with 25% (v/v) phosphoric acid solution to a pH of 3.5 (USP 1-Aug-2024) .

Standard solution: 0.1 mg/mL of USP Pentobarbital RS in Mobile phase

(USP 1-Aug-2024)

Sample solution: 0.1 mg/mL of Pentobarbital in Mobile phase. Sonicate to dissolve if necessary. (USP 1-Aug-2024)

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 1.8 times the retention time of pentobarbital (USP 1-Aug-2024)

3.2 System suitability

Sample: Standard solution

Suitability requirements

(USP 1-Aug-2024)

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73% (USP 1-Aug-2024)

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pentobarbital (C₁₁H₁₈N₂O₃) in the portion of Pentobarbital taken:

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

r_U = peak response of pentobarbital (USP 1-Aug-2024) from the Sample solution

r_S = peak response of pentobarbital (USP 1-Aug-2024) from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% (USP 1-Aug-2024) on the dried basis; and 97.0%–102.0% (USP 1-Aug-2024) on the dried basis, where the material is labeled as intended solely for veterinary use

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

Organic Impurities

Mobile phase: Prepare as directed in the Assay.

Standard solution: 0.001 mg/mL of USP Pentobarbital RS in Mobile phase

Sensitivity solution: 0.0005 mg/mL of USP Pentobarbital RS from the Standard solution, in Mobile phase (USP 1-Aug-2024) Sample solution: 1 mg/mL of Pentobarbital in Mobile phase

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 214 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2.0 times the retention time of pentobarbital (USP 1-Aug-2024)

4.2 System suitability

Samples: Standard solution and Sensitivity solution

[Note—The relative retention times in Table 1 are provided as information that could aid in peak assignment.]

Table 1 (USP 1-Aug-2024)

a 6-Imino-5-ethyl-5-(1-methylbutyl)barbituric acid.

b 5-Ethyl-5-(1-ethylpropyl)barbituric acid.

c 5-Ethyl-5-(1,3-dimethylbutyl)barbituric acid.

Suitability requirements

(USP 1-Aug-2024)

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 5.0%, (USP 1-Aug-2024) Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Aug-2024)

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any specified and unspecified (USP 1-Aug-2024) impurity in the portion of Pentobarbital taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × 100

r_U = peak response of any specified or unspecified (USP 1-Aug-2024) impurity from the Sample solution

r_S = peak response of (USP 1-Aug-2024) pentobarbital from the Standard solution

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

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

F = relative response factor of the impurity (see Table 2 (USP 1-Aug-2024) )

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2 (USP 1-Aug-2024)

a Where the material is labeled as intended solely for veterinary use, the limit of pentobarbital ethyl analog (USP 1-Aug-2024) is NMT (USP 1-Aug-2024) 3.0%.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 1.0%

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Pentobarbital RS