Zolpidem Tartrate Extended-Release Tablets
DEFINITION
Zolpidem Tartrate Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of zolpidem tartrate (C42H48N6O8).
IDENTIFICATION
•  A. Ultraviolet Absorption 197U
Sample:  25 µg/mL of zolpidem tartrate in 0.01 M hydrochloric acid from a suitable quantity of powder obtained by grinding 1 Tablet
•  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:  3.3 mL of phosphoric acid in 1 L of water. Adjust with triethylamine to a pH of 5.5.
Mobile phase:  Acetonitrile, methanol, and Buffer (4:5:11)
Standard stock solution:  0.5 mg/mL of USP Zolpidem Tartrate RS in a mixture of alcohol and 0.01 M hydrochloric acid (4:1)
Standard solution:  0.1 mg/mL of USP Zolpidem Tartrate RS in Mobile phase from the Standard stock solution
Sample stock solution:  Finely powder NLT 8 Tablets. Transfer the powder quantitatively to a suitable volumetric flask to obtain 0.5 mg/mL of zolpidem tartrate. Add 70% of the flask volume of a mixture of alcohol and 0.01 M hydrochloric acid (5:2), and stir on a magnetic stirrer for 1 h. Dilute with alcohol to volume. Allow solid particles to settle, and pass the supernatant through a suitable filter (Whatman 40 or equivalent).
Sample solution:  0.1 mg/mL of zolpidem tartrate from filtered Sample stock solution in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 240 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Column temperature:  40
Flow rate:  1 mL/min
Injection size:  15 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 the labeled amount of zolpidem tartrate (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
Change to read:
•  Dissolution 711
Test 1(RB 1-Jul-2011) 
Medium:  0.01 N hydrochloric acid; 500 mL
Apparatus 1:  100 rpm
Times:  30, 90, and 240 min
Standard solution:  Solution of USP Zolpidem Tartrate RS in Medium containing (L/500) mg/mL, where L is the label claim in mg/Tablet
Sample solution:  Pass a portion of the solution under test through a suitable filter.
Detector:  UV 295 nm
Cell path:  1 cm
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of zolpidem tartrate (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== label claim (mg/Tablet)
V== volume of Medium, 500 mL
Tolerances:  See Table 1.
Table 1
Time
(min)
Amount
Dissolved
30 50%–70%
90 70%–90%
240 NLT 85%
The percentages of the labeled amount of zolpidem tartrate (C42H48N6O8) dissolved in the times specified conform to Acceptance Table 2 in Dissolution 711.
Test 2:  If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium, Apparatus, and Times:  Proceed as directed for Test 1.
Standard solution:  Solution of USP Zolpidem Tartrate RS in Medium containing (L/500) mg/mL, where L is the label claim in mg/Tablet
Sample solution:  Pass a portion of the solution under test through a suitable filter.
Detector:  UV 295 nm
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of zolpidem tartrate (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== label claim (mg/Tablet)
V== volume of Medium, 500 mL
Tolerances:  See Table 2.
Table 2
Time
(min)
Amount
Dissolved
30 55%–75%
90 70%–90%
240 NLT 85%
The percentages of the labeled amount of zolpidem tartrate (C42H48N6O8) dissolved in the times specified conform to Acceptance Table 2 in Dissolution 711.
Test 3:  If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:  0.01 N hydrochloric acid; 500 mL
Apparatus 1:  100 rpm
Times:  30, 90, and 120 min
Standard solution:  Solution of USP Zolpidem Tartrate RS in Medium containing (L/500) mg/mL, where L is the label claim in mg/Tablet
Sample solution:  Pass a portion of the solution under test through a suitable filter.
Detector:  UV 237 nm
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of zolpidem tartrate (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== label claim (mg/Tablet)
V== volume of Medium, 500 mL
Tolerances:  See Table 3.
Table 3
Time
(min)
Amount
Dissolved
30 25%–45%
90 65%–85%
120 NLT 80%
The percentages of the labeled amount of zolpidem tartrate (C42H48N6O8) dissolved in the times specified conform to Acceptance Table 2 in Dissolution 711.(RB 1-Jul-2011)
•  Uniformity of Dosage Units 905: Meet the requirements
IMPURITIES
Change to read:
•  Organic Impurities
Buffer, Mobile phase, Standard stock solution, Sample solution, and Chromatographic system:  Proceed as directed in the Assay.
System suitability solution:  Dissolve a suitable amount of USP Zolpidem Related Compound A RS in Standard stock solution to obtain a solution containing 1 µg/mL of zolpidem related compound A. Dilute 1 mL of the resulting solution with Mobile phase to 5 mL.
System suitability 
Sample:  System suitability solution
Suitability requirements 
Resolution:  NLT 1.5 between zolpidem related compound A and zolpidem
Tailing factor:  NMT 3.0 for the zolpidem peak
Relative standard deviation:  NMT 2.0% for the zolpidem peak
Analysis 
Sample:  Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rT) × (1/F) × 100
rU== peak response for each impurity from the Sample solution
rT== sum of the peak responses for all the peaks from the Sample solution
F== relative response factor of the corresponding impurity from Table 4
Acceptance criteria:  See Table 4.
Table 4
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
Zolpidem acida 0.3 1.2(RB 1-Jul-2011) 0.20
Zolpidem related compound Ab 0.9 1.0 0.20
Zolpidem 1.0
Any unspecified degradation
product
1.0 0.20
Total impurities 0.5
a  2-(6-Methyl-2-p-tolylimidazo[1,2-a]pyridin-3-yl)acetic acid.
b  N,N-Dimethyl-2-(7-methyl-2-p-tolylimidazo[1,2-a]pyridin-3-yl)acetamide.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.
Add the following:
•  Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.(RB 1-Jul-2011)
•  USP Reference Standards 11
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
USP Zolpidem Tartrate RS Click to View Structure
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