Eszopiclone Tablets

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 Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of eszopiclone (C₁₇H₁₇ClN₆O₃).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Standard: USP Eszopiclone RS

Sample: Nominally 37.5 mg of eszopiclone from Tablets prepared as follows. Powder a number of Tablets, and mix the resulting powder.

Transfer a portion of powder, equivalent to 37.5 mg of eszopiclone, to a suitable container, add 30 mL of acetone, and shake. Dilute with acetone to 50 mL and pass the resulting solution through a suitable filter. Evaporate the filtrate to dryness on a water bath and dry the residue in an oven at 60° for 2 h.

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

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

Mobile phase: Acetonitrile and Solution A (25:75) adjusted with dilute phosphoric acid to a pH of 6.5 ± 0.05

Standard stock solution: 0.5 mg/mL of USP Eszopiclone RS prepared as follows. Transfer a suitable quantity of USP Eszopiclone RS to an appropriate volumetric flask and add 50% of the final flask volume of acetonitrile. Sonication may be used to promote dissolution. Dilute with acetonitrile to volume.

Standard solution: 0.03 mg/mL of USP Eszopiclone RS from Standard stock solution in Mobile phase passed through a suitable filter of 0.45-μm pore size. Use the filtrate.

Sample stock solution: Nominally 0.2 mg/mL of eszopiclone from Tablets prepared as follows. Transfer NLT 5 intact Tablets to a suitable volumetric flask. Add 5% of the final flask volume of Solution A and sonicate in cool water for 5 min with constant shaking. Add 30% of the final flask volume of acetonitrile and sonicate for 15 min. Dilute with acetonitrile to volume. Centrifuge the resulting solution and use the supernatant.

Sample solution: Nominally 0.03 mg/mL of eszopiclone from Sample stock solution in Mobile phase passed through a suitable filter of 0.45-μm pore size. Use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 303 nm

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

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

Run time: NLT 1.9 times the retention time of eszopiclone

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 the labeled amount of eszopiclone (C₁₇H₁₇ClN₆O₃) in the portion of Tablets 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 = nominal concentration of eszopiclone in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

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

Mobile phase: Acetonitrile and Solution A (30:70) adjusted with dilute phosphoric acid (1 in 10) to a pH of 6.5 ± 0.05

Standard stock solution: 0.1 mg/mL of USP Eszopiclone RS in acetonitrile. Sonication may be used to promote dissolution.

Standard solution: (L/500) mg/mL of USP Eszopiclone RS from Standard stock solution in Medium, where L is the Tablet label claim in mg.

Pass the resulting solution through a suitable filter of 0.45-μm pore size and use the filtrate.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 303 nm

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

Column temperature: 30°

Flow rate: 1.2 mL/min

Injection volume: 100 μL

Run time: NLT 1.5 times the retention time of eszopiclone

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 the labeled amount of eszopiclone (C₁₇H₁₇ClN₆O₃) dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × 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)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Acceptance criteria: NLT 80% (Q) of the labeled amount of eszopiclone (C₁₇H₁₇ClN₆O₃) is dissolved.

Test 2

Medium: 0.1 N hydrochloric acid VS; 500 mL

Apparatus 2: 50 rpm

Time: 20 min

Buffer: To each liter of water add 1.0 mL of phosphoric acid and adjust with 2 N sodium hydroxide TS to a pH of 4.0.

Mobile phase: Acetonitrile and Buffer (20:80)

Standard stock solution: 0.1 mg/mL of USP Eszopiclone RS in Medium. Sonication may be used to promote dissolution.

Standard solution: (L/500) mg/mL of USP Eszopiclone RS from Standard stock solution in Medium, where L is the label claim in mg/Tablet.

Pass the resulting solution through a suitable filter of 0.45-μm pore size and use the filtrate.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 303 nm

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

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 80 μL

Run time: NLT 1.5 times the retention time of eszopiclone

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 the labeled amount of eszopiclone (C₁₇H₁₇ClN₆O₃) dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × 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)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of eszopiclone (C₁₇H₁₇ClN₆O₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

Organic Impurities

Protect all solutions from light.

Solution A: 8.1 g/L of sodium dodecyl sulfate and 6.9 g/L of monobasic sodium phosphate in water. Sonicate for NLT 15 min and do not let the temperature of the water bath exceed 25°. Pass the resulting solution through a suitable filter of 0.45-μm pore size. Foam may form during filtration.

Mobile phase: Acetonitrile and Solution A (37:63) adjusted with dilute phosphoric acid (1 in 100) to a pH of 4.8 ± 0.05

Diluent: Acetonitrile and Solution A (37:63) adjusted with dilute phosphoric acid (1 in 100) to a pH of 2.5 ± 0.05

System suitability solution: 0.008 mg/mL each of USP Eszopiclone Related Compound A RS and USP Eszopiclone RS in Diluent. Sonication may be used to promote dissolution.

Standard solution: 0.008 mg/mL of USP Eszopiclone RS in Diluent passed through a suitable membrane filter of 0.45-μm pore size. Use the filtrate. Sonication may be used to promote dissolution.

Sample solution: Nominally 0.8 mg/mL of eszopiclone in Diluent prepared as follows. Crush NLT 20 Tablets to a fine powder and transfer a suitable portion to an appropriate volumetric flask. Add 60% of the final flask volume of Diluent, sonicate for 15 min in cold water with periodic shaking, and dilute with Diluent to volume. Pass the resulting solution through a suitable membrane filter of 0.45-μm pore size, and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 303 nm

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

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

Run time: NLT 2 times the retention time of eszopiclone

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 10 between eszopiclone related compound A and eszopiclone, System suitability solution

Tailing factor: NMT 2.0 for eszopiclone, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

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

r_U = peak response of each degradation product 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 = nominal concentration of eszopiclone in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. Disregard peaks less than 0.04%.

Table 1

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

6 ADDITIONAL REQUIREMENTS

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

Labeling: The labeling states the Dissolution test used only if Test 1 is not used.

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