Zolpidem Tartrate

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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(C₁₉H₂₁N₃O)₂·C₄H₆O₆ 764.87

Imidazo[1,2-a]pyridine-3-acetamide, N,N,6-trimethyl-2-(4-methylphenyl)-, [R-(R*,R*)]-2,3-dihydroxy butanedioate;

N,N,6-Trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-acetamide L-(+)-tartrate CAS RN^®: 99294-93-6; UNII: WY6W63843K.

1 DEFINITION

Zolpidem Tartrate contains NLT 98.0% and NMT 102.0% of zolpidem tartrate [(C₁₉H₂₁N₃O)₂·C₄H₆O₆], calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K (CN 1-May-2020)

Sample: Dissolve 0.10 g of Zolpidem Tartrate in 10 mL of 0.1 M hydrochloric acid. Add 10 mL of water. Add dropwise with stirring 1 mL of diluted ammonia solution. Filter and collect the resulting precipitate. Wash the precipitate with water, and then dry at 100°-105° for 2 h. Use 2 mg of the dried residue.

Analysis: The IR spectrum of the free base thus obtained corresponds to the IR spectrum of similarly prepared USP Zolpidem Tartrate RS.

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

C. REACTION OF TARTRATES

Sample: 0.1 g of Zolpidem Tartrate

Analysis: Dissolve the Sample in 1 mL of methanol with gentle heating. To 0.1 mL of the solution, add 0.1 mL of a 100-g/L solution of potassium bromide, 0.1 mL of a 20-g/L solution of Resorcinol, and 3 mL of sulfuric acid. Heat on a water bath for 5-10 min. A dark blue color develops. Allow to cool, then pour the solution into water.

Acceptance criteria: The dark blue color changes to red.

3 ASSAY

3.1 PROCEDURE

Buffer: 5.6 g/L of phosphoric acid. Adjust with triethylamine to a pH of 5.5.

Mobile phase: Methanol, acetonitrile, and Buffer (23:18:59)

System suitability solution: 0.05 mg/mL each of USP Zolpidem Tartrate RS and USP Zolpidem Related Compound A RS in Mobile phase

Standard solution: 0.1 mg/mL of USP Zolpidem Tartrate RS in Mobile phase

Sample solution: 0.1 mg/mL of Zolpidem Tartrate in Mobile phase

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 15-cm; 4-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 3 times the retention time of zolpidem

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

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

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of zolpidem tartrate [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] in the portion of Zolpidem Tartrate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of zolpidem from the Sample solution

r_S = peak response of zolpidem from the Standard solution

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

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

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Buffer, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.001 mg/mL of USP Zolpidem Tartrate RS in Mobile phase

Sample solution: 0.5 mg/mL of Zolpidem Tartrate in Mobile phase

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

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

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Zolpidem Tartrate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of zolpidem from the Standard solution

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

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

Acceptance criteria: See Table 1. Disregard any peak less than 0.05%.

Table 1

^a Counter ion peak; not to be reported and not to be included in total impurities.

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method I, Method la: NMT 3.0%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, and store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Zolpidem Tartrate RS

USP Zolpidem Related Compound A RS

N,N-Dimethyl-2-(7-methyl-2-p-tolylimidazo[1,2-a]pyridin-3-yl)acetamide.

C₁₉H₂₁N₃O 307.39