Tramadol Hydrochloride and Acetaminophen Compounded Oral Suspension

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

Tramadol Hydrochloride and Acetaminophen Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amounts of tramadol hydrochloride (C₁₆H₂₅NO₂·HCl) and acetaminophen (C₈H₉NO₂).

Prepare Tramadol Hydrochloride and Acetaminophen Compounded Oral Suspension containing 7.5 mg/mL of tramadol hydrochloride and 65 mg/mL of acetaminophen as follows (see Pharmaceutical Compounding-Nonsterile Preparations 〈795〉).

ᵃ Ultracet 37.5-mg/325-mg tablets, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ.

ᵇ Paddock Laboratories, Minneapolis, MN.

Calculate the required quantity of each ingredient for the total amount to be prepared. Place the required number of Tramadol Hydrochloride and Acetaminophen tablets in a suitable mortar, and comminute to a fine powder. Add the Vehicle in small portions, and triturate to make a smooth paste. Add increasing volumes of the Vehicle to make a tramadol hydrochloride and acetaminophen liquid that is pourable. Transfer the contents of the mortar, stepwise and quantitatively, to a calibrated bottle. Add enough of the Vehicle to bring to final volume, and mix well.

2 ASSAY

2.1 Tramadol Hydrochloride

Solution A: 20 mM of phosphoric acid and 4 g/L of sodium 1-hexane sulfonate

Mobile phase: Acetonitrile and Solution A (50:50). Filter and degas.

Diluent: Acetonitrile and water (50:50)

Standard solution: 0.15 mg/mL of USP Tramadol Hydrochloride RS in Diluent

Sample solution: Shake thoroughly by hand each bottle of Oral Suspension. Prepare 0.15 mg/mL of tramadol hydrochloride from Oral Suspension and Diluent, and centrifuge.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 275 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1.0 mL/min
• Injection volume: 5 µL

System suitability

• Sample: Standard solution
• [Note-The retention time for tramadol hydrochloride is about 6 min.]
• Suitability requirements
• Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tramadol hydrochloride (C₁₆H₂₅NO₂·HCl) in the portion of Oral Suspension 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%

2.2 Acetaminophen

Mobile phase: Acetonitrile and water (70:30). Filter and degas.

Standard solution: 65 µg/mL of USP Acetaminophen RS in Mobile phase

Sample solution: Shake thoroughly by hand each bottle of Oral Suspension. Prepare 65 µg/mL of acetaminophen from Oral Suspension and Mobile phase, and centrifuge.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 275 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1.0 mL/min
• Injection volume: 5 µL

System suitability

• Sample: Standard solution
• [Note-The retention time for acetaminophen is about 2 min.]
• Suitability requirements
• Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) in the portion of Oral Suspension 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 Acetaminophen RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of acetaminophen in the Sample solution (µg/mL)

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 3.8–4.8

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in tight, light-resistant containers. Store in a refrigerator or at controlled room temperature.

Beyond-Use Date: NMT 90 days after the date on which it was compounded, when stored in a refrigerator or at controlled room temperature

Labeling: Label to indicate that it is to be well shaken before use, and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Acetaminophen RS

USP Tramadol Hydrochloride RS