Pentazocine and Acetaminophen 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

Pentazocine and Acetaminophen Tablets contain an amount of Pentazocine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of pentazocine (C₁₉H₂₇NO) and NLT 90.0% and NMT 110.0% of the labeled amount of acetaminophen (C₈H₉NO₂). 

2 IDENTIFICATION

A. Thin-Layer Chromatographic Identification Test 〈201〉

Diluent: Chloroform and methanol (1:1)

Standard solution A: 1 mg/mL of USP Pentazocine RS in Diluent

Standard solution B: 26 mg/mL of USP Acetaminophen RS in Diluent

Sample solution: Transfer a quantity of finely powdered Tablets, nominally equivalent to about 5 mg of pentazocine and 130 mg of acetaminophen, to a suitable flask. Add 5 mL of Diluent, shake, and allow the solids to settle. Use the supernatant.

2.1 Chromatographic system

Developing solvent system: Ethyl acetate, methanol, and formic acid (90:5:5)

Spray reagent: Dissolve 300 mg of platinic chloride in 100 mL of water and add 100 mL of potassium iodide solution (6 in 100). Analysis: Evaporate the solvents in cool, circulating air. After developing and examining the spots, spray the plate with Spray reagent. Acceptance criteria: The R values, size, and intensity of color of the two principal spots of the Sample solution correspond to those of F

Standard solution A and Standard solution B.

2.2 ASSAY

2.3 Pentazocine

Mobile phase: Chloroform, methanol, and isopropylamine (960:40:2)

Diluent: Methanol and 0.035 N sulfuric acid (1:1)

Standard stock solution: 0.5 mg/mL of USP Pentazocine RS in Diluent

Standard solution: Transfer 10.0 mL of the Standard stock solution to a 125-mL separator. Add 30 mL of water and 5 mL of sodium carbonate solution (1:10). Extract with 60 mL of chloroform and pass the chloroform layer through filter paper, collecting the filtrate in a 100-mL volumetric flask. Dilute with chloroform to volume and mix.

Sample solution: Transfer an amount nominally equivalent to 25 mg of pentazocine, from NLT 20 finely powdered Tablets, to a 50-mL glass stoppered cylinder. Add 50.0 mL of Diluent and shake intermittently for 15 min. Sonicate for about 2 min, allow the solids to settle, and transfer 10.0 mL of the supernatant to a 125-mL separator. [Note—Save the remainder of the supernatant for use in the Assay for Acetaminophen. Minimize the waiting period before this test is performed to prevent significant hydrolysis of acetaminophen to p aminophenol.]

Add 30 mL of water and 5 mL of sodium carbonate solution (1:10) to the separator and mix. Extract with 60 mL of chloroform and pass the chloroform layer through filter paper, collecting the filtrate in a 100-mL volumetric flask. Dilute with chloroform to volume and mix.

2.3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 25-cm; 10-µm packing L3

Flow rate: 1.2 mL/min

Injection volume: 20 µL

2.3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 3.0

Relative standard deviation: NMT 2.0%

2.3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pentazocine (C₁₉H₂₇NO) in the portion of Tablets taken:

Result = (r_U /r_S) × (C_S /C_U ) × 100

r_U = peak response of pentazocine from the Sample solution

r_S = peak response of pentazocine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

2.4 Acetaminophen

[Note—Minimize the time between the addition of the Diluent and the injection of the Sample solution to prevent significant hydrolysis of acetaminophen to p-aminophenol.]

Mobile phase: Chloroform, methanol, and isopropylamine (960:40:2)

Diluent: Methanol and 0.035 N sulfuric acid (1:1)

Standard stock solution: 13 mg/mL of USP Acetaminophen RS in Diluent

Standard solution: Dilute 2.0 mL of the Standard stock solution with ethyl acetate to 200 mL.

Sample solution: Dilute 2.0 mL of the supernatant reserved from the Assay for Pentazocine immediately with ethyl acetate to volume in a 200-mL volumetric flask to minimize hydrolysis of acetaminophen to p-aminophenol and mix.

2.4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 10-µm packing L3

Flow rate: 1.4 mL/min

Injection volume: 10 µL

2.4.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 3.0

Relative standard deviation: NMT 2.0%

2.4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of acetaminophen (C₈H₉NO₂) in the portion of Tablets taken:

Result = (r_U /r_S) × (C /C_U ) × 100

r_U = peak response of acetaminophen from the Sample solution

r_S = peak response of acetaminophen from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

3 PERFORMANCE TESTS

Change to read:

Uniformity of Dosage Units 〈905〉: Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Diluent: Acetonitrile and 0.035 N sulfuric acid (6:4)

Mobile phase: Tetrahydrofuran, phosphoric acid, and 0.005 M monobasic sodium phosphate (50:1:950)

Pentazocine standard stock solution: 0.25 mg/mL of USP Pentazocine RS in Diluent

System suitability stock solution: 0.325 mg/mL of USP Acetaminophen RS in Diluent

System suitability solution: Transfer 1.0 mL of the System suitability stock solution to a 100-mL volumetric flask. Add 5.0 mL of the Pentazocine standard stock solution, dilute with Mobile phase to volume, and mix.

Standard solution: Transfer a quantity of USP Acetaminophen RS to a suitable volumetric flask. Add a sufficient volume of Pentazocine standard stock solution and mix to dissolve the acetaminophen. Dilute with Mobile phase to volume. Mix to obtain known concentrations of 0.0125 and 0.325 mg/mL of pentazocine and acetaminophen, respectively.

Sample stock solution: Transfer 1 Tablet to a 100-mL volumetric flask, add 50 mL of Diluent, and sonicate for 30 min. Dilute with Diluent to volume, and mix. Pass a portion of this solution through a paper filter, covering the funnel with a watch glass and discarding the first few mL of the filtrate.

Sample solution: Dilute 5.0 mL of the Sample stock solution with Mobile phase to 100 mL and pass this solution through a membrane filter of 0.5-µm or finer pore size.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 9.4-mm × 10-cm; 5-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 10 µL

3.2 System suitability

Sample: System suitability solution

[Note—The relative retention times for acetaminophen and pentazocine are 0.2 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 7 between pentazocine and acetaminophen

Relative standard deviation: NMT 2.0% for the pentazocine and acetaminophen peaks

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pentazocine (C₁₉H₂₇NO) and acetaminophen (C₈H₉NO₂) in the portion of Tablets taken:

Result = (r_U /r_S) × (C_S /C_U ) × 100

r_U = peak response of pentazocine or acetaminophen from the Sample solution

r_S = peak response of pentazocine or acetaminophen from the Standard solution

C_S = concentration of the appropriate USP Reference Standard (USP Pentazocine RS or USP Acetaminophen RS) in the Standard solution (mg/mL)

C_U = nominal concentration of pentazocine or acetaminophen in the Sample solution (mg/mL)

(CN 1-Aug-2023)

4 IMPURITIES

4-Aminophenol in Acetaminophen-Containing Drug Products 〈227〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Acetaminophen RS

USP Pentazocine RS