Zolpidem Tartrate Tablets

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

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

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1 DEFINITION

Zolpidem Tartrate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of zolpidem tartrate [(C₁₉H₂₁N₃O)₂·C₄H₆O₆].

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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: 3.4 g/L of monobasic potassium phosphate in water, adjusted with ammonium hydroxide to a pH of 5.5

Mobile phase: Acetonitrile, methanol, and Buffer (30:20:50)

Standard stock solution: 0.8 mg/mL of USP Zolpidem Tartrate RS in 0.01 N hydrochloric acid TS

Standard solution: 0.16 mg/mL of USP Zolpidem Tartrate RS in Mobile phase, from the Standard stock solution

Sample stock solution: Nominally 0.4 mg/mL of zolpidem tartrate from NLT 20 Tablets prepared as follows. Transfer the Tablets to a suitable volumetric flask and add 40% of the flask volume of 0.125 N hydrochloric acid TS. Mix well until the Tablets disintegrate, and 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.¹

Sample solution: Nominally 0.16 mg/mL of zolpidem tartrate in Mobile phase, from the Sample stock solution

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

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

Flow rate: 1.2 mL/min

Injection volume: 10 µL

Run time: NLT 2.5 times the retention time of zolpidem tartrate

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 3.0 for zolpidem

Relative standard deviation: NMT 2.0% for zolpidem

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zolpidem tartrate [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] 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 zolpidem tartrate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: 0.01 N hydrochloric acid TS; 900 mL, deaerated

Apparatus 2: 50 rpm

Time: 15 min

Perform the analysis by using either the Spectrophotometric procedure or the Chromatographic procedure.

Spectrophotometric procedure (USP 1-Aug-2020)

Standard solution: (L/1000) mg/mL of USP Zolpidem Tartrate RS 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.

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 [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] 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 USP Zolpidem Tartrate RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Chromatographic procedure

Solution A: 5.6 g/L of phosphoric acid in water, adjusted with triethylamine to a pH of 5.5

Mobile phase: Acetonitrile, methanol, and Solution A (18:23:59)

Standard solution: (L/900) mg/mL of USP Zolpidem Tartrate RS in Medium, where L is the label claim of zolpidem tartrate in mg/Tablet. Sonicate as needed.

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: 3.9-mm × 15-cm; 4-µm packing L1

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 1.5 times the retention time of zolpidem tartrate

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 [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] dissolved:

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

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL (USP 1-Aug-2020)

Tolerances: NLT 80% (Q) of the labeled amount of zolpidem tartrate [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] is dissolved.

4.1.2 Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid VS; 900 mL

Apparatus 2: 50 rpm

Time: 20 min

Standard solution: (L/900) mg/mL of USP Zolpidem Tartrate RS 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.

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 [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] 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 USP Zolpidem Tartrate RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of zolpidem tartrate artrate [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] is dissolved.

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 TS; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Standard solution: (L/900) mg/mL of USP Zolpidem Tartrate RS 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.

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 [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] 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 USP Zolpidem Tartrate RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 85% (Q) of the labeled amount of zolpidem tartrate [(C₁₉H₂₁N₃O)₂·C₄H₆O₆] is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A: 3.3 mL/L of phosphoric acid in water, adjusted with triethylamine to a pH of 6.0

Solution B: Acetonitrile

Solution C: Methanol

Mobile phase: See Table 1.

Table 1

Diluent: Solution B, Solution C, and Solution A (15:10:75)

System suitability solution: 0.5 mg/mL of USP Zolpidem Tartrate RS and 0.0008 mg/mL of USP Zolpidem Related Compound A RS in Diluent

Standard solution: 0.005 mg/mL of USP Zolpidem Tartrate RS in Diluent

Sample solution: Nominally equivalent to 0.5 mg/mL of zolpidem tartrate in Diluent from NLT 10 Tablets, prepared as follows. Transfer the Tablets to a suitable volumetric flask, add 70% of the flask volume of Diluent, and stir for 30 min. Dilute with Diluent to volume. Centrifuge a portion of the solution and use the clear supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 15-cm; 4-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between zolpidem and zolpidem related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of zolpidem from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 4-Oxo-4-(p-tolyl)butanoic acid.

^b Process impurities related to specific manufacturing process of the drug substance; included for peak identification purposes only and are not to be reported or included in the total degradation products.

^c 2-(6-Methyl-2-p-tolylimidazo[1,2-α]pyridin-3-yl)acetic acid.

^d N,N-Dimethyl-4-oxo-4-(p-tolyl)butanamide.

^e N,N-Dimethyl-2-(6-methyl-2-p-tolylimidazo[1,2-α]pyridin-3-yl)-2-oxoacetamide.

^f N,N-Dimethyl-4-oxo-4-(p-tolyl)but-2-enamide.

^g 3-Bromo-N,N-dimethyl-4-oxo-4-(p-tolyl)butanamide.

^h 4-Methyl-N-(5-methylpyridin-2-yl)benzamide.

ⁱ 6-Methyl-2-p-tolylimidazo[1,2-α]pyridine-3-carbaldehyde.

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 Tartrate RS

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

¹ The Whatman #40 filter or equivalent may be suitable.