Zolpidem Tartrate Tablets
DEFINITION
Zolpidem Tartrate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of zolpidem tartrate (C42H48N6O8).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
:
The spectrum of the Sample solution in the test for Dissolution matches that of the Standard solution.
197U:
The spectrum of the Sample solution in the test for Dissolution matches that of the Standard solution.
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
3.4 g/L of monobasic potassium phosphate in water, adjusted with ammonium hydroxide to a pH of 5.5
Mobile phase:
Acetonitrile, methanol, and Buffer (3:2:5)
Standard stock solution:
0.8 mg/mL of USP Zolpidem Tartrate RS in 0.01 M hydrochloric acid
Standard solution:
0.16 mg/mL of USP Zolpidem Tartrate RS in Mobile phase from the Standard stock solution
Sample stock solution:
Transfer NLT 20 Tablets to a suitable volumetric flask to obtain a solution having a concentration of 0.4 mg/mL of zolpidem tartrate. Add 40% of the flask volume of 0.125 N hydrochloric acid. Mix well until the Tablets disintegrate, then add 50% of the flask volume of Mobile phase. Dilute with water to volume, and stir for 30 min using a magnetic stirrer. Allow solid particles to settle, and pass the supernatant through a suitable filter (e.g. Whatman No. 40 filter or equivalent).
Sample solution:
0.16 mg/mL of zolpidem tartrate from filtered Sample stock solution and Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.2 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 3.0 for zolpidem
Relative standard deviation:
NMT 2.0% for zolpidem
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C42H48N6O8 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Zolpidem Tartrate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
0.01 N hydrochloric acid; 900 mL, deaerated
Apparatus 2:
50 rpm
Time:
15 min
Sample solution:
Pass a portion of the solution through a suitable filter of 0.45-µm pore size.
Standard solution:
(L/1000) mg/mL of USP Zolpidem Tartrate RS in Medium, where L is the Tablet label claim, in mg
Detection:
UV 295 nm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of C42H48N6O8 dissolved:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = Tablet label claim (mg) |
| V | = | = volume of Medium (mL), 900 |
Tolerance:
NLT 80% (Q) of the labeled amount of C42H48N6O8 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer, Mobile phase, Standard stock solution, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
System suitability solution:
2 mg/mL of USP Zolpidem Impurities Mixture RS, prepared by dissolving the weighed amount of USP Zolpidem Impurities Mixture RS in 10% of the flask volume of 0.01 N hydrochloric acid, and diluting with Mobile phase to volume.
Standard solution:
8 µg/mL of USP Zolpidem Tartrate RS in Mobile phase from the Standard stock solution
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 1.5 between zolpidem related compound B and zolpidem related compound C, System suitability solution
Tailing factor:
NMT 2.0 for the zolpidem peak, Standard solution
Relative standard deviation:
NMT 10.0% for the zolpidem peak, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of 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:
See Impurity Table 1.
Total impurities:
NMT 0.5%
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|
| Zolpidem acida | 0.23 | 0.3 | |
| Zolpidem related compound Bb | 0.58 | 0.3 | |
| Zolpidem related compound Cc | 0.70 | 0.3 | |
| Zolpidem tartrate | 1.0 | — | |
| Zolpidem carbaldehyded | 1.45 | 0.3 | |
| Any individual unspecified degradation product | — | 0.2 | |
|
a
2-(6-Methyl-2-p-tolylimidazo[1,2-
 ]pyridin-3-yl)acetic acid.
b
N,N-Dimethyl-2-(6-methyl-2-p-tolylimidazo[1,2-a]pyridin-3-yl)-2-oxoacetamide.
c
4-Methyl-N-(5-methylpyridin-2-yl)benzamide.
d
6-Methyl-2-p-tolylimidazo[1,2-
]pyridine-3-carbaldehyde.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Zolpidem Impurities Mixture RS
Contains at least 98.5% of zolpidem tartrate; 0.2% of zolpidem tartrate related compound B (N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-(2-oxoacetamide)); and 0.2% of zolpidem tartrate related compound C (5-methyl-2-(4-methylbenzamido)pyridine).
Contains at least 98.5% of zolpidem tartrate; 0.2% of zolpidem tartrate related compound B (N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-(2-oxoacetamide)); and 0.2% of zolpidem tartrate related compound C (5-methyl-2-(4-methylbenzamido)pyridine).
USP Zolpidem Tartrate RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 5083
Pharmacopeial Forum: Volume No. 35(4) Page 883