Printed on: Tue Aug 03 2021, 07:49:40 AM Official Status: Currently Official on 03-Aug-2021 DocId: 1_GUID-7DD0E791-F289-458E-9774-7300EC99BC84_4_en-US

(EST)
Printed by: Le Tran Official Date: Official as of 01-May-2020 Document Type: USP @2021 USPC
1

System suitability
Zolpidem Tartrate 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
Analysis
Samples: Standard solution and Sample solution
(C19H21N3O)2 · C4H6O6 764.87 Calculate the percentage of zolpidem tartrate
Imidazo[1,2-a]pyridine-3-acetamide, N,N,6-trimethyl-2-(4- [(C19H21N3O)2 · C4H6O6] in the portion of Zolpidem
methylphenyl)-, [R-(R*,R*)]-2,3-dihydroxy butanedioate; Tartrate taken:
N,N,6-Trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-
acetamide L-(+)-tartrate [99294-93-6]. Result = (r U/r S) × (C S/C U) × 100
DEFINITION rU = peak response of zolpidem from the Sample
Zolpidem Tartrate contains NLT 98.0% and NMT 102.0% of solution
zolpidem tartrate [(C19H21N3O)2 · C4H6O6], calculated on the rS = peak response of zolpidem from the Standard
anhydrous basis. solution
CS = concentration of USP Zolpidem Tartrate RS in the
IDENTIFICATION Standard solution (mg/mL)

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Change to read: CU = concentration of Zolpidem Tartrate in the
Sample solution (mg/mL)
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
Spectroscopy: 197A or 197K▲ (CN 1-May-2020) Acceptance criteria: 98.0%–102.0% on the anhydrous
Sample: Dissolve 0.10 g of Zolpidem Tartrate in 10 mL of basis
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
ci IMPURITIES
• RESIDUE ON IGNITION á281ñ: NMT 0.1%
• ORGANIC IMPURITIES
water, and then dry at 100°–105° for 2 h. Use 2 mg of the
Buffer, Mobile phase, System suitability solution, and
dried residue.
Chromatographic system: Proceed as directed in the
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Analysis: The IR spectrum of the free base thus obtained
Assay.
corresponds to the IR spectrum of similarly prepared USP
Standard solution: 0.001 mg/mL of USP Zolpidem
Zolpidem Tartrate RS.
Tartrate RS in Mobile phase
• B. The retention time of the major peak of the Sample
Sample solution: 0.5 mg/mL of Zolpidem Tartrate in Mobile
solution corresponds to that of the Standard solution, as
phase
obtained in the Assay.
System suitability
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• C. REACTION OF TARTRATES
Samples: System suitability solution and Standard solution
Sample: 0.1 g of Zolpidem Tartrate
[NOTE—See Table 1 for the relative retention times.]
Analysis: Dissolve the Sample in 1 mL of methanol with
Suitability requirements
gentle heating. To 0.1 mL of the solution, add 0.1 mL of a
Resolution: NLT 2.0 between zolpidem related
100-g/L solution of potassium bromide, 0.1 mL of a
compound A and zolpidem, System suitability solution
20-g/L solution of resorcinol, and 3 mL of sulfuric acid. Heat
Relative standard deviation: NMT 10.0%, Standard
on a water bath for 5–10 min. A dark blue color develops.
solution
Allow to cool, then pour the solution into water.
Analysis
Acceptance criteria: The dark blue color changes to red.
Samples: Standard solution and Sample solution
ASSAY Calculate the percentage of each impurity in the portion of
• PROCEDURE Zolpidem Tartrate taken:
Buffer: 5.6 g/L of phosphoric acid. Adjust with
triethylamine to a pH of 5.5. Result = (r U/r S) × (C S/C U) × 100
Mobile phase: Methanol, acetonitrile, and Buffer
(23:18:59) rU = peak response of each impurity from the Sample
System suitability solution: 0.05 mg/mL each of USP solution
Zolpidem Tartrate RS and USP Zolpidem Related rS = peak response of zolpidem from the Standard
Compound A RS in Mobile phase solution
Standard solution: 0.1 mg/mL of USP Zolpidem Tartrate RS CS = concentration of USP Zolpidem Tartrate RS in the
in Mobile phase Standard solution (mg/mL)
Sample solution: 0.1 mg/mL of Zolpidem Tartrate in Mobile CU = concentration of Zolpidem Tartrate in the
phase Sample solution (mg/mL)
Chromatographic system
(See Chromatography á621ñ, System Suitability.) Acceptance criteria: See Table 1. Disregard any peak less
Mode: LC than 0.05%.
Detector: UV 254 nm
Column: 3.9-mm × 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

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Printed on: Tue Aug 03 2021, 07:49:40 AM Official Status: Currently Official on 03-Aug-2021 DocId: 1_GUID-7DD0E791-F289-458E-9774-7300EC99BC84_4_en-US
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Printed by: Le Tran Official Date: Official as of 01-May-2020 Document Type: USP @2021 USPC
2

Table 1 SPECIFIC TESTS

Relative Acceptance • WATER DETERMINATION á921ñ, Method I, Method Ia: NMT
Retention Criteria, 3.0%
Name Time NMT (%)
ADDITIONAL REQUIREMENTS
Tartaric acida 0.16 — • PACKAGING AND STORAGE: Preserve in well-closed
Zolpidem related com- containers, and store at controlled room temperature.
pound A 0.83 0.10 • USP REFERENCE STANDARDS á11ñ
Zolpidem 1.0 —
USP Zolpidem Tartrate RS
USP Zolpidem Related Compound A RS
Any individual
— N,N-Dimethyl-2-(7-methyl-2-p-tolylimidazo[1,2-a]
impurity 0.10 pyridin-3-yl)acetamide.
Total impurities — 0.2 C19H21N3O 307.39
a Counter ion peak; not to be reported and not to be included in total impurities.

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