Eszopiclone

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

Eszopiclone contains NLT 98.5% and NMT 101.0% of eszopiclone (C₁₇H₁₇ClN₆O₃), 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 second peak of the System suitability solution, as obtained in the Limit of R-Isomer test.

3 ASSAY

Procedure

Solution A: 1.4 g/L of anhydrous dibasic sodium phosphate in water

Mobile phase: Acetonitrile and Solution A (25:75) adjusted with phosphoric acid to a pH of 6.5

Standard stock solution: 1 mg/mL of USP Eszopiclone RS prepared as follows. Transfer a suitable quantity of USP Eszopiclone RS to an appropriate volumetric flask and add 15% of the final flask volume of acetonitrile. Add 15% of the final flask volume of Mobile phase.

Sonication may be used to promote dissolution. Dilute with Mobile phase to volume.

Standard solution: 0.2 mg/mL of USP Eszopiclone RS from Standard stock solution in Mobile phase

Sample stock solution: 1 mg/mL of Eszopiclone prepared as follows. Transfer a suitable quantity of Eszopiclone to an appropriate volumetric flask and add 15% of the final flask volume of acetonitrile. Add 15% of the final flask volume of Mobile phase. Sonication may be used to promote dissolution. Dilute with Mobile phase to volume.

Sample solution: 0.2 mg/mL of Eszopiclone from Sample stock solution in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 303 nm

Column: 4.6-mm × 15.0-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 2.5 times the retention time of eszopiclone

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of eszopiclone (C₁₇H₁₇ClN₆O₃) in the portion of Eszopiclone 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 Eszopiclone RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.5%–101.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.10%

Organic Impurities

Solution A: 8.1 g/L of sodium lauryl sulfate and 2.1 g/L of monobasic sodium phosphate in water

Mobile phase: Acetonitrile and Solution A (628:1000) adjusted with phosphoric acid to a pH of 4.0

System suitability solution: 0.04 mg/mL each of USP Eszopiclone Related Compound A RS and USP Eszopiclone RS in Mobile phase.

Sonication may be used to promote dissolution.

Standard stock solution: 0.4 mg/mL of USP Eszopiclone RS in Mobile phase. Sonication may be used to promote dissolution.

Standard solution: 0.004 mg/mL of USP Eszopiclone RS from Standard stock solution in Mobile phase

Sample solution: 4 mg/mL of Eszopiclone in Mobile phase. Sonication may be used to promote dissolution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: 2.7 times the retention time of eszopiclone

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between eszopiclone related compound A and eszopiclone, System suitability solution

Tailing factor: NMT 1.5 for eszopiclone, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of eszopiclone from the Standard solution

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

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

Acceptance criteria: See Table 1. Disregard peaks below 0.05%.

Table 1

^a 6-(5-Chloropyridin-2-yl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one.

Limit of R-Isomer

Mobile phase: 1 mL of diethylamine in 1000 mL of absolute alcohol. Sonication may be used to promote dissolution.

System suitability solution: 0.5 mg/mL of USP Eszopiclone RS and 0.1 mg/mL of USP Zopiclone R-Isomer RS prepared as follows. Transfer suitable amounts of USP Eszopiclone RS and USP Zopiclone R-Isomer RS to an appropriate volumetric flask. Add 20% of the flask volume of dichloromethane. Sonication may be used to promote dissolution. Dilute with absolute alcohol to volume.

Sample solution: 0.5 mg/mL of Eszopiclone prepared as follows. Transfer a suitable amount of Eszopiclone to an appropriate volumetric flask. Add 20% of the flask volume of dichloromethane. Sonication may be used to promote dissolution. Dilute with absolute alcohol to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 303 nm

Column: 4.6-mm × 25.0-cm; 5-μm packing L40

Flow rate: 0.5 mL/min

Injection volume: 20 μL

Run time: NLT 1.3 times the retention time of eszopiclone

System suitability

Sample: System suitability solution

[Note—The relative retention times of zopiclone R-isomer and eszopiclone are about 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between zopiclone R-isomer and eszopiclone

Analysis

Sample: Sample solution

Calculate the percentage of zopiclone R-isomer in the portion of Eszopiclone taken:

Result = (r_U/r_T) × 100

r_U = peak response of zopiclone R-isomer from the Sample solution

r_T = sum of the peak responses from the Sample solution

Acceptance criteria: NMT 0.30%

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° under vacuum for 3 h.

Acceptance criteria: NMT 0.50%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Eszopiclone RS

USP Eszopiclone Related Compound A RS

[Note—This material may be available in the free base or salt form.]

6-(5-Chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate 4-oxide.

C₁₇H₁₇ClN₆O₄ 404.81

6-(5-Chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate 4-oxide, 3-chlorobenzoate (ERR 1-Jun-2018) salt (1:1).

C₁₇H₁₇ClN₆O₄ · C₇H₅ClO₂  (ERR 1-Jun-2018) 561.38

USP Zopiclone R-Isomer RS

(R)-6-(5-Chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate.

C₁₇H₁₇ClN₆O₃ 388.81