(zol' pi dem tar' trate).
(C19H21N3O)2· C4H6O6 764.87
Imidazo[1,2-a]pyridine-3-acetamide, N,N,6-trimethyl-2-(4-methylphenyl)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate;
N,N,6-Trimethyl-2-p-tolylimidazo[1,2-a]pyridine-3-acetamide l-(+)-tartrate [99294-93-6].
Zolpidem Tartrate contains NLT 98.5% and NMT 101.0% of C42H48N6O8, calculated on the anhydrous basis.
• A. Infrared Absorption 197K
Sample: Dissolve 0.10 g in 10 mL of 0.1 M hydrochloric acid. Add 10 mL of water. Add dropwise with stirring 1 mL of dilute ammonia. Filter and collect the resulting precipitate. Wash the precipitate with water, and then dry at 100105 for 2 h. Use 2 mg of the dried residue to make the KBr pellet.
Analysis: The IR spectrum of the free base thus obtained corresponds to the IR spectrum of a similarly prepared KBr pellet with 2 mg of USP Zolpidem RS free base.
• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the test for Organic Impurities.
• 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 510 min. A dark blue color develops. Allow to cool, then pour the solution into water.
Acceptance criteria: The dark blue color changes to red.
Sample solution: Dissolve 0.300 g of Zolpidem Tartrate in a mixture of 20 mL of anhydrous acetic acid and 20 mL of acetic anhydride.
(See Titrimetry 541.)
Mode: Direct titration
Titrant: 0.1 N perchloric acid VS
Endpoint detection: Potentiometric
Sample: Sample solution
Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Carry out a blank titration.
Calculate the percentage of C42H48N6O8 in the portion of Zolpidem Tartrate taken:
Result = [(V B) × N × F/W] × 100
Acceptance criteria: 98.5%101.0% on the anhydrous basis
Buffer: 5.6 g/L phosphoric acid in water. 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: 1 µg/mL of USP Zolpidem Tartrate RS in Mobile phase
Sample solution: 0.5 mg/mL of Zolpidem Tartrate in Mobile phase
Detector: UV 254 nm
Column: 3.9-mm × 15-cm; 4-µm packing L1
Flow rate: 1.5 mL/min
Injection size: 20 µL
Samples: System suitability solution and Standard solution
Resolution: NLT 2.0 between zolpidem tartrate related compound A and zolpidem tartrate, System suitability solution
Relative standard deviation: NMT 10.0%, Standard solution
Samples: Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Zolpidem Tartrate taken:
Result = (rU/rS) × (CS/CU) × 100
Individual impurities: NMT 0.10%
Total impurities: NMT 0.2%
[NoteDisregard any peak with an area less than 0.25 times that of the principal peak from the Standard solution (0.05%) and any peak with a relative retention time of 0.16, which is due to tartaric acid. ]
• Water Determination, Method Ia 921: NMT 3.0%
• Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.
• USP Reference Standards 11
USP Zolpidem Related Compound A RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 5082Pharmacopeial Forum: Volume No. 34(6) Page 1487