Etomidate 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

Etomidate Injection is a sterile, nonpyrogenic solution. It contains NLT 90.0% and NMT 110.0% of the labeled amount of etomidate (C₁₄H₁₆N₂O₂). It may contain suitable buffers and preservatives.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970

Sample solution: 10 µg/mL of etomidate in isopropyl alcohol

Medium: Isopropyl alcohol

Acceptance criteria: 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

Buffer: 0.7 g/L of monobasic sodium phosphate in water

Mobile phase: Acetonitrile and Buffer (2:3)

Standard solution: 0.16 mg/mL of USP Etomidate RS in acetonitrile

Sample solution: Nominally 0.16 mg/ml of etomidate from Injection in acetonitrile

Chromatographic system

(See Chromatography (621) System Suitability)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 2.3 mL/min

Injection volume: 20 µL

Run time: NLT 3 times the retention time of etomidate

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 20

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of etomidate (C₁₄H₁₆N₂O₂) in the portion of Injection taken:

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

r_U = peak response from the Sample solution

r_S = peak response the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

ORGANIC IMPURITIES, PROCEDURE 1: RELATED COMPOUNDS

Solution A: Dissolve 6 g of sodium citrate dihydrate and 4 g of anhydrous citric acid in 1 L of water.

Solution B: Acetonitrile

Mobile phase: See Table 1

Diluent: Weigh 6 g of sodium citrate dihydrate and 4 g of anhydrous citric acid into a 1000-mL volumetric flask. Add 500 mL of water, and shake to dissolve. Add 110 mL of acetonitrile and 50 mL of methanol, and dilute with water to volume.

System suitability selution: 0.02 mg/m each of Ettidale RS and USP Metornistate Hidrochluinnt

Standard stock solution: 0.1 mg/ml, of USP Metornidate Hydrochloride RS in methanich

Standard solution: 0.004 mg/mL of USP Metomadate tydrochloride RS from the Standard stock solution in Diluent

Sensitivity solution: 0.8 µg/mL of USP Metomistate Hydrochloride RS from the Stanıtan solution in hent

Sample solution: Nominally 0.8 mg/ml, of etomidate from Injection in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm 30-cm; packing L1

Flow rate: 2.0 mL/min

Injection volume: 50 μL

System suitability

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

Suitability requirements

Resolution: NLT 2.0 betiveen etomidate and melomidale, System suttality aplution

Relative standard deviation: NMT 3.0, Standard solution

Signal-to-noise ratio: NLT 10.Sensitivity solution

Analysis

Samples: Standards and Sample solution

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

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

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of metomidate from the Standard solution

C_S = concentration of USP Metomidate Hydmchiuride RS in the Stanstand solution (mg/ml)

C_U = concentration of Etomidatie in the Sample solution (mg/ml)

M_r1 = molecular weight of metomidate free base, 230.26

M_r2 = molecular weight of metomidate hydrochloride, 266.72

Acceptance criteria: Son Jab No-Disregant any impurity peaks less than 0.09%

^a 1-(1-Phenylethyl)-1H-imidazole-5-carboxylic acid.

^b This is quantitated in Organic Impurities, Procedure 2: Total Propylene Glycol Esters.

^c Methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate.

Organic Impurities, Procedure 2: Total Propylene Glycol Esters: [Note—Perform this test if propylene glycol is used in the formulation.]

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 1.6 μg/mL of USP Etomidate RS in acetonitrile

Standard solution: 0.025 mg/mL of USP Etomidate RS in acetonitrile

Sample solution: Nominally 1.6 mg/mL of etomidate from Injection in acetonitrile

System suitability

Samples: Senativity solution and Standard solution

Suitability requirements

Tailing factor: NMT 2.0, Standart spition

Relative standard deviation: NMT 2.0, Standard solution

Signal-to-noise ratio: NLT 10. Sensity solution

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of etomidate from the Standard solution

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

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

F = relative response factor for each individual impurity (see Table 3)

Acceptance criteria: See Table 3. Disregard any impurity peaks less than 0.05%.

^a This is quantitated in Organic Impurities, Procedure 1: Related Compounds.

^b 2-Hydroxypropyl ester and 2-hydroxy-1-methylethyl ester.

^c Total impurities include all impurities from Table 2 and Table 3.

5 SPECIFIC TESTS

Bacterial Endotoxins Test (8): It contains NMT 8.35 USP Endotoxin Units/mg of etomidate.

Sterility Tests (71), Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

pH (791): Between 4.0 and 7.0

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

Other Requirements: It meets the requirements in Injections and Implanted Drug Products  (1).

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose containers. Store at controlled room temperature.