Zaleplon Capsules

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

Zaleplon Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of zaleplon (C₁₇H₁₅N₅O).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum 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: 0.3 g/L of ammonium formate in water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1
 

Diluent: Acetonitrile and water (20:80)

Standard solution: 0.1 mg/mL of USP Zaleplon RS in Diluent

Sample solution: Nominally 0.1 mg/mL of zaleplon from NLT 5 Capsules in Diluent. Pass through a lter of 0.45-µm pore size. [Note—Use the entire Capsule with its contents. Shake for 10 min.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identication B, use a diode array detector in the range of 210–400 nm.

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

Column temperature: 30°

Flow rate: 1.4 mL/min

Injection volume: 15 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zaleplon (C₁₇H₁₅N₅O) in the portion of Capsules 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 Zaleplon RS in the Standard solution (mg/mL)

C_u = nominal concentration of zaleplon in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution

Test 1

Medium: Water; 900 mL

Apparatus 2: 75 rpm, with sinkers if necessary

Time: 20 min

Determine the percentage of zaleplon dissolved using one of the following procedures.

Spectrophotometric procedure

Standard stock solution: 0.044 mg/mL of USP Zaleplon RS prepared as follows. Transfer a suitable quantity of USP Zaleplon RS to an appropriate volumetric ask. Add 10.0% of the total ask volume of methanol to dissolve. Dilute with Medium to volume. [Note—This solution is stable for 7 days.]

Standard solution: (L/1000) mg/mL of USP Zaleplon RS from Standard stock solution in Medium, where L is the label claim in mg/Capsule. [Note—This solution is stable for 7 days.]

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: About 333 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zaleplon (C₁₇H₁₅N₅O) dissolved:

Result = (A_u /A_s ) × (C_s /L) × V × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Chromatographic procedure

Buffer: 0.77 g/L of ammonium acetate in water

Mobile phase: Methanol and Buffer (33:67)

Standard stock solution: 0.22 mg/mL of USP Zaleplon RS prepared as follows. Dissolve rst in methanol using 5% of total ask volume and dilute with Medium to volume.

Standard solution: (L/900) mg/mL of USP Zaleplon RS from Standard stock solution in Medium, where L is the label claim in mg/Capsule

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 5-cm; 3-µm packing L1

Column temperature: 35°

Flow rate: 2.0 mL/min

Injection volume: 50 µL

Run time: 2 times the retention time of zaleplon

System suitability

Sample: Standard solution

Suitability requirements

Column eciency: NLT 2000 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zaleplon (C₁₇H₁₅N₅O) dissolved:

Result = (r_u /r_s ) × (C_s /L) × V × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Zaleplon RS in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 85% (Q) of the labeled amount of zaleplon (C₁₇H₁₅N₅O) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium: Water; 900 mL

Apparatus 2: 75 rpm, with sinkers

Time: 20 min

Buffer: 1.36 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (30:70)

Standard stock solution: 1.1 mg/mL of USP Zaleplon RS in Mobile phase

Standard solution: (L/900) mg/mL of USP Zaleplon RS from Standard stock solution in Medium, where L is the label claim in mg/Capsule

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 28°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: 2 times the retention time of zaleplon

System suitability

Sample: Standard solution

Suitability requirements

Column eciency: NLT 2000 theoretical plates

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 zaleplon (C₁₇H₁₅N₅O) dissolved:

Result = (r_u /r_s ) × (C_s /L) × V × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Zaleplon RS in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of zaleplon (C₁₇H₁₅N₅O) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution: 0.5 mg/mL of USP Zaleplon RS in Diluent

System suitability solution: 0.5 µg/mL of USP Zaleplon Related Compound B RS and 0.5 mg/mL of USP Zaleplon RS in Diluent

Sensitivity solution: 0.05 µg/mL of USP Zaleplon RS in Diluent, from the Standard stock solution

Standard solution: 0.1 mg/mL of USP Zaleplon RS in Diluent, from the Standard stock solution

System suitability

Samples: System suitability solution and Sensitivity solution

Suitability requirements

Resolution: NLT 1.5 between zaleplon and zaleplon related compound B, System suitability solution

Tailing factor: NMT 1.5 for the zaleplon peak, System suitability solution

Relative standard deviation: NMT 2.0% for the zaleplon peak, System suitability solution

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

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of any individual degradation product in the portion of Capsules taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of any individual degradation product from the Sample solution

r_s = peak response of USP Zaleplon RS from the Standard solution

C_s = concentration of USP Zaleplon RS in the Standard solution (mg/mL)

C_u = nominal concentration of zaleplon in the Sample solution (mg/mL)

Acceptance criteria: See Table 2.

Table 2

^a 3-Aminopyrazole-4-carbonitrile.

^b This is a process impurity that is included in the table for identication purposes only. It is controlled in the drug substance and is not to be reported or included in the total degradation products for the drug product.

^c (E)-N-{3-[3-(Dimethylamino)acryloyl]phenyl}-N-ethylacetamide.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in light-resistant containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Zaleplon RS

USP Zaleplon Related Compound B RS

N-[3-(3-Cyanopyrazolo[1,5-a]pyrimidin-5-yl)phenyl]-N-ethylacetamide.

C₁₇H₁₅N₅O       305.33