Zolpidem Tartrate
(zol' pi dem tar' trate).
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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-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 100–105 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 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.
•  Procedure
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.
Titrimetric system 
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
V== sample titrant volume (mL)
B== blank titrant volume (mL)
N== titrant normality (meq/mL)
F== 382.4 mg/meq
W== sample weight (mg)
Acceptance criteria:  98.5%–101.0% on the anhydrous basis
Inorganic Impurities 
•  Residue on Ignition 281: NMT 0.1%
Organic Impurities 
•  Procedure
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
Chromatographic system 
Mode:  LC
Detector:  UV 254 nm
Column:  3.9-mm × 15-cm; 4-µm packing L1
Flow rate:  1.5 mL/min
Injection size:  20 µL
System suitability 
Samples:  System suitability solution and Standard solution
Suitability requirements 
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
rU== peak response for each impurity from the Sample solution
rS== peak response for zolpidem from the Standard solution
CS== concentration of USP Zolpidem Tartrate RS in the Standard solution (mg/mL)
CU== concentration of Zolpidem Tartrate in the Sample solution (mg/mL)
Acceptance criteria 
Individual impurities:  NMT 0.10%
Total impurities:  NMT 0.2%
[Note—Disregard 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. ]
•  Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.
•  USP Reference Standards 11
USP Zolpidem RS Click to View Structure
USP Zolpidem Related Compound A RS
    C19H21N3O        307.39
USP Zolpidem Tartrate RS Click to View Structure
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Topic/Question Contact Expert Committee
Monograph Hariram Ramanathan, M.S.
Associate Scientific Liaison
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
USP35–NF30 Page 5082
Pharmacopeial Forum: Volume No. 34(6) Page 1487