Etomidate

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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1H-Imidazole-5-carboxylic acid, 1-(1-phenylethyl)-, ethyl ester, (+)-;

(+)-Ethyl 1-(α-methylbenzyl)imidazole-5-carboxylate CAS RN^®: 33125-97-2; UNII: Z22628B598.

1 DEFINITION

Etomidate contains NLT 98.0% and NMT 102.0% of etomidate (C₁₄H₁₆N₂O₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION Tests (197), Infrared Spectroscopy: 197K

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 (40:60)

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

Sample solution: 0.16 mg/ml of Etomidate in acetonitrile

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 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 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of etomidate (C₁₄H₁₆N₂O₂) in the portion of Etomidate 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: 98.0%-102.0% on the dried basis

4 IMPURITIES

Residue on Ignition (281): NMT 0.1%

Organic Impurities

Solution A: Dissolveig of sodium citrate dihydrate and of antyhos chuc acid of

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Weigh 5 g of sodium citane dihydrate and 4 g of anhydrous choc acid into a 1000-mt volumetric flask. Add 500 ms of water and shake to dissolve. Add 110 ml of actual and 50 ml of cuttanel and be with to vokame

System sultability solution: 0.02 mg/ml. each of USP Etomidate RS and Metomitate itydrochloride 3 in Wuent

Standard solution: 0.004 mg/m of USP Metomidale Hydrochloride RS in Duent

Sensitivity solution: 0.8 µg/ms of USP Metomidate Hydrochloride RS from the Standard solution in Diluent

Sample solution: 0.8 mg/mL of Etormidate in Diluent

Chromatographic system

(See Chromatosrauby 10:21. Sestem Surtab

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 2.0 mL/me

Injection volume: 50 μL

System suitability

Bumples: System sutability solution, Standard solution, and Sensivily solation

Sultability requirements

Resolution: NLT 2.0 between ecomidate and metomaciate, System sutability solution

Relative standard deviation: NMT 3.0%, Standard solution

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

Analysis

Samples: Shandon solution and Sample solution

Calculate the percentage of each impurity in the portion of Etomidate 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: Ses Tatile 2 [Note-Disregard any impurity peaks less than 0.05%]

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

^b Methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate

5 SPECIFIC TESTS

Loss on Drying (731)

Sample: 1 g of Etomidate

Analysis: Dry the Sample over phosphorus pentoxide for 16 h.

Acceptance criteria: NMT 0.5%

OPTICAL ROTATION (781S), Procedures, Specific Rotation

Sample solution: 10 mg/mL of Etomidate in dehydrated alcohol

Acceptance criteria: 67.0°–70.0° (t = 20°), calculated on the dried basis

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well closed, light-resistant containers, and store at room temperature.