Tramadol Hydrochloride 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

Tramadol Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of tramadol hydrochloride (C₁₆H₂₅NO₂ · HCl).

2 IDENTIFICATION

Change to read:

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample solution: Transfer powdered Tablets, equivalent to 200 mg of tramadol hydrochloride, into a 50-mL volumetric flask, add 20 mL of dichloromethane, and sonicate. Filter, and transfer the clear supernatant to a separating funnel. Extract the dichloromethane layer with two 10-mL portions of 2 N sodium hydroxide, and discard the aqueous layer. Dry the dichloromethane layer over anhydrous sodium sulfate, and filter. Evaporate this solution to dryness under a stream of nitrogen.

Acceptance criteria: Meet the requirements

2.2 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

Solution A: Dissolve 5 mL of perchloric acid in 950 mL of water in a 1-L volumetric flask. Add 4 mL of 25% ammonia water, dilute with water to volume, and mix. Adjust with 25% ammonia water to a pH of 2.2 ± 0.2.

Mobile phase: Acetonitrile and Solution A (23:77)

Standard solution: 0.1 mg/mL of USP Tramadol Hydrochloride RS in 0.1 N hydrochloric acid

Sample solution: Finely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 50 mg of tramadol hydrochloride, into a 100-mL volumetric flask. Add 70 mL of 0.1 N hydrochloric acid, sonicate for 5 min, and shake for 10 min. Dilute with 0.1 N hydrochloric acid to volume, and mix. Pass a portion of this solution through a suitable filter, discarding the first 20 mL of the filtrate. Transfer 10 mL of the clear filtrate into a 50-mL volumetric flask, dilute with 0.1 N hydrochloric acid to volume, and mix.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 273 nm
• Column: 3.9-mm × 15-cm; packing L7
• Flow rate: 2 mL/min
• Injection size: 20 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tramadol hydrochloride (C₁₆H₂₅NO₂ · HCl) 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 Tramadol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of tramadol hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Solution A, Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard solution: 0.055 mg/mL of USP Tramadol Hydrochloride RS in Medium

Sample solution: Withdraw 9 mL from the dissolution vessel, and pass through a suitable filter. Discard the first 3 mL of the filtrate.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tramadol hydrochloride (C₁₆H₂₅NO₂ · HCl) dissolved:

Result = (rᵤ/rₛ) × (Cₛ/L) × V × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Tramadol Hydrochloride 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 tramadol hydrochloride (C₁₆H₂₅NO₂ · HCl) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

4.3 Procedure for content uniformity

Solution A, Mobile phase, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample solution: Transfer 1 whole Tablet to a 100-mL volumetric flask, add 70 mL of 0.1 N hydrochloric acid, sonicate until the Tablet is completely disintegrated, and shake for 10 min. Dilute with 0.1 N hydrochloric acid to volume, and mix. Pass a portion of this solution through a suitable filter, discarding the first 20 mL of the filtrate. Transfer 10 mL of the clear filtrate into a 50-mL volumetric flask, dilute with 0.1 N hydrochloric acid to volume, and mix.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tramadol hydrochloride (C₁₆H₂₅NO₂ · HCl) in the Tablet 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 Tramadol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of tramadol hydrochloride in the Sample solution (mg/mL)

5 IMPURITIES

5.1 Organic Impurities

5.1.1 Procedure

Solution A and Mobile phase: Prepare as directed in the Assay.

System suitability solution: 0.2 mg/mL each of USP Tramadol Hydrochloride RS and USP Tramadol Related Compound A RS in Mobile phase

Standard solution: 6 µg/mL of USP Tramadol Hydrochloride RS in Mobile phase

System sensitivity solution: Transfer 5 mL of the Standard solution into a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Sample solution: Finely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 200 mg of tramadol hydrochloride, into a 50-mL volumetric flask. Add about 35 mL of Mobile phase, sonicate for 5 min, and shake for 10 min. Dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a suitable filter, and use the filtrate.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 273 nm
• Column: 3.9-mm × 15-cm; packing L7
• Flow rate: 1 mL/min
• Injection size: 20 µL

System suitability

• Samples: System suitability solution, Standard solution, and System sensitivity solution
• Suitability requirements
• Resolution: NLT 2.0 between tramadol related compound A and tramadol, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution; NMT 10%, System sensitivity 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) × (1/F) × 100

rᵤ = peak response of each individual impurity from the Sample solution

rₛ = peak response of tramadol from the Standard solution

Cₛ = concentration of USP Tramadol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of tramadol hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Impurity Table 1)

[Note-Disregard any peak that is shown to be due to solvents or excipients.]

Acceptance criteria

Individual unspecified impurities: See Impurity Table 1.

Impurity Table 1

ᵃ Tramadol related compound A.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Tramadol Hydrochloride RS

USP Tramadol Related Compound A RS