Zaleplon

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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C₁₇H₁₅N₅O      305.33

Acetamide,N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethyl-;3′-(3-Cyanopyrazolo[1,5-a]pyrimidin-7-yl)-N-ethylacetanilide CAS RN: 151319-34-5; UNII: S62U433RMH.

1 DEFINITION

Zaleplon contains NLT 98.0% and NMT 102.0% of zaleplon (C₁₇H₁₅N₅O), calculated on the anhydrous 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 Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Buffer: 0.3 g/L of ammonium formate in water. Adjust with formic acid to a pH of 4.0.

Mobile phase: Acetonitrile and Buffer (7:18)

Diluent: Acetonitrile and water (1:1)

System suitability solution: 0.5 mg/mL of USP Zaleplon RS and 0.5 µg/mL each of USP Zaleplon Related Compound A RS and USP Zaleplon

Related Compound B RS in Diluent

Standard solution: 50 µg/mL of USP Zaleplon RS in Diluent

Sample solution: 50 µg/mL of Zaleplon in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 245 nm

Column: 4-mm x 10-cm; 3-um packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: 2 times the retention time of zaleplon

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for zaleplon and zaleplon related compound B are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 2.0 between zaleplon and zaleplon related compound B, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of zaleplon (C₁₇H₁₅N₅O) in the portion of Zaleplon taken:

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

r_u = peak response of zaleplon from the Sample solution

r_s = peak response of zaleplon from the Standard solution

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

C_u = concentration of Zaleplon in the Sample solution (µg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Organic Impurities

Solution A: 1.4 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 3.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (250:750)

System suitability solution: 0.5 mg/mL of USP Zaleplon RS and 0.5 µg/mL each of USP Zaleplon Related Compound A RS, USP Zaleplon

Related Compound B RS, and USP Zaleplon Related Compound C RS in Diluent

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

Sample solution: 500 µg/mL of Zaleplon in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 15-cm; 5-µm packing L7

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.2 between zaleplon related compound A and zaleplon related compound C; NLT 2.0 between zaleplon and zaleplon related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Zaleplon taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of any individual impurity from the Sample solution

r_s = peak response of zaleplon from the Standard solution

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

C_u = concentration of Zaleplon in the Sample solution (µg/mL)

F = relative response factor for the corresponding impurity peak (see Table 2)

Acceptance criteria: See Table 2. Disregard any peak below 0.05%.

Table 2

^a 3-Aminopyrazole-4-carbonitrile.

^b Process impurity; may not be found in all manufacturing processes.

^c N-[3-(3-Cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide.

^d (E)-N-[3-(3-Cyano-6-{3-[3-(N-ethylacetamido)phenyl]-3-oxoprop-1-en-1-yl}pyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in light-resistant containers, and store at room temperature.

USP Reference Standards 〈11〉

USP Zaleplon RS

USP Zaleplon Related Compound A RS

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

C₁₅H₂₀N₂O₂       260.33

USP Zaleplon Related Compound B RS

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

C₁₇H₁₅N₅O         305.33

USP Zaleplon Related Compound C RS

7-[3-(N-Ethylacetamido)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide.

C₁₇H₁₇N₅O₂        323.35