Zolpidem Tartrate Extended-Release Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Zolpidem Tartrate Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970 (CN 1-MAY-2020)

Sample: 25 µg/mL of zolpidem tartrate in 0.01 M hydrochloric acid from a suitable quantity of powder obtained by grinding 1 Tablet

Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 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 from the Standard stock solution in Mobile phase

Sample stock solution: Finely powder NLT 8 Tablets. Transfer the powder quantitatively to a suitable volumetric flask to obtain nominally 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).

Alternatively, the Sample stock solution can be prepared as follows. Transfer NLT 20 Tablets to a suitable volumetric flask to obtain a nominal concentration of 0.5 mg/mL of zolpidem tartrate. Add 10% of the flask volume of alcohol and stir for 30 min or until the Tablets have completely disintegrated. Add another 10% of the flask volume of alcohol and stir for another 90 min. Add 10% of the flask volume of 0.01 M hydrochloric acid followed by 40% of the flask volume of a mixture of alcohol and 0.01 M hydrochloric acid (5:2). Continue to stir for another 30 min. Remove the stirrer bar and rinse with alcohol. Dilute with alcohol to volume.

Sample solution: Nominally 0.1 mg/mL of zolpidem tartrate from filtered Sample stock solution in Mobile phase. If the Sample stock solution is prepared using the alternative procedure, dilute the required volume of the Sample stock solution with Mobile phase and centrifuge instead of filtering before use.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 15 µL

3.3 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 = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Zolpidem Tartrate RS in the Standard solution (mg/mL)

C_U = nominal concentration of the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

4.1.1 Test 1

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

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved:

Result = (A_U/A_S) x (C_S/L) x V x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg /mL)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: See Table 1.

Table 1

The percentages of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.2 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 in 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.

Instrumental conditions

Mode: UV

Analytical wavelength: 295 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved:

Result = (A_U/A_S) x (C_S/L) x V x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: See Table 2.

Table 2

The percentages of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.3 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.

Instrumental conditions

Mode: UV

Analytical wavelength: 237 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved:

Result = (A_U/A_S) x (C_S/L) x V x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V volume of Medium, 500 mL

Tolerances: See Table 3.

Table 3

The percentages of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.4 Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

Medium: 0.01 N hydrochloric acid: 500 mL

Apparatus 1: 100 rpm

Times: 30, 60, 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. Replace the volume withdrawn with an equal volume of Medium.

Instrumental conditions

Mode: UV

Analytical wavelength: 294 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at each time point (Q):

Q₃₀ = (A_U/A_S) x C_S x V x (1/L) x 100

Q₆₀ = [(A_U/A_S) x C_S x V x (1/L) ×100] + [Q₃₀ x (V_S/V)]

Q₁₂₀ = [(A_U/A_S) x C_S x V x (1/L) ×100] + [(Q₃₀ +Q₆₀) x (V_S/V)]

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Zolpidem Tartrate RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

V_S = volume of the sample withdrawn (mL)

Tolerances: See Table 4.

Table 4

The percentages of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.5 Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.

Medium: pH 6.8 phosphate buffer (Dissolve 6.8 g of monobasic potassium phosphate and 0.8 g of sodium hydroxide in 1 L of water. Adjust with phosphoric acid or 1 N sodium hydroxide to a pH of 6.8.); 900 mL

Apparatus 1: 50 rpm

Times: 60, 180, and 360 min

Buffer: Dissolve 5.6 g of phosphoric acid in 1 L of water. Adjust with triethylamine to a pH of 5.5.

Mobile phase: Methanol, acetonitrile, and Buffer (28:22:50)

Standard stock solution: 0.5 mg/mL of USP Zolpidem Tartrate RS in methanol

Standard solution: (L/900) mg/mL of USP Zolpidem Tartrate RS from Standard stock solution in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 7.5-cm; 3.5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 25 µL

Run time: NLT 2.5 times the retention time of zolpidem

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response of the Sample solution

r_S = peak response of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: See Table 5.

Table 5

The percentages of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at the times specified conform to Dissolution (711). Acceptance Table 2.

4.1.6 Test 6: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.

Medium: 0.01 N hydrochloric acid: 500 mL

Apparatus 1: 100 rpm

Times: 15, 60, and 120 min

Diluent: Methanol and water (50:50)

Standard stock solution: 0.25 mg/mL of USP Zolpidem Tartrate RS in Diluent. Sonication may be used to aid complete dissolution.

Standard solution: (L/500) mg/mL of USP Zolpidem Tartrate RS from Standard stock solution in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Replace the volume withdrawn with an equal volume of Medium.

Instrumental conditions

Mode: UV

Analytical wavelength: 295 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration of zolpidem tartrate (C₄₂H₄₈N₆O₈) in the sample withdrawn at each time point (i):

C_i = (A_U/A_S) x C_S

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

Calculate the percentage of the labeled amount (Q_i) of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at each time point (i):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = [(C₂ x V) + (C₁ x V_S)] x (1/L) x 100

Result = {(C₃ x V) + [(C₂ + C₁) x V_S]} x (1/L) x 100

C_i = concentration of zolpidem tartrate in the portion of sample withdrawn at time point i (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn from the Medium (mL)

Tolerances: See Table 6.

Table 6

The percentages of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.1.7 Test 7: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.

Medium: 0.01 N hydrochloric acid; 500 mL

Apparatus 1: 100 rpm

Times: 30, 90, and 240 min

Standard stock solution: 0.5 mg/mL of USP Zolpidem Tartrate RS in methanol. Sonication may be used to aid complete dissolution.

Standard solution: 0.0125 mg/mL of USP Zolpidem Tartrate RS from Standard stock solution in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-um pore size. Discarding the first 2 mL of filtrate.

Instrumental conditions

Mode: UV

Analytical wavelength: 237 nm

Cell: 5.0 mm

Blank: Medium

Analysis

Samples: Standard solution, Sample solution, and Blank

Correct the instrument by using the Blank.

Calculate the concentration (C_i) of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at each time point (i):

C_i = (A_U/A_S) x C_S

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at each time point (i):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = {[C₂ x (V - V_S)] + (C₁ x V_S) x (1/L) x 100

Result = ({C₃ x [V - (2 x V_S)]} + [(C₂ + C₁) x V_S]) x (1/L) x 100

C_i = concentration of zolpidem tartrate in the portion of sample withdrawn at the specified time point i (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 7.

Table 7

The percentages of the labeled amount of zolpidem tartrate (C₄₂H₄₈N₆O₈) dissolved at the times specified conform to Dissolution (711), Acceptance Table 2.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

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 the 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 = (r_U/r_T) x (1/F) x 100

r_U = peak response for each impurity from the Sample solution

r_T = sum of all the peak responses from the Sample solution

F = relative response factor of the corresponding impurity (see Table 8)

Acceptance criteria: See Table 8.

Table 8

^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.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, and store at controlled room temperature.

6.2 LABELING

When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

6.3 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