Ketorolac Tromethamine 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

Ketorolac Tromethamine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of ketorolac tromethamine (C₁₅H₁₃NO₃· C₄H₁₁NO₃).

2 IDENTIFICATION

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

B. The UV absorption spectra of the ketorolac peak of the Sample solution and that of the Standard solution exhibit maxima and minima at

the same wavelengths, as obtained in the Assay.

3 ASSAY

Procedure

Mobile phase: Methanol, water, and glacial acetic acid (55:44:1)

Diluent: Methanol and water (1:1). [Note—Protect all volumetric solutions from light.]

Standard stock solution: 0.24 mg/mL of USP Ketorolac Tromethamine RS in methanol

Standard solution: 24 μg/mL of USP Ketorolac Tromethamine RS in Diluent from Standard stock solution

System suitability stock solution: 25 μg/mL each of USP Ketorolac Related Compound A RS, USP Ketorolac Related Compound B RS, USP

Ketorolac Related Compound C RS, and USP Ketorolac Related Compound D RS in methanol

System suitability solution: 0.25 μg/mL each of USP Ketorolac Related Compound A RS, USP Ketorolac Related Compound B RS, USP

Ketorolac Related Compound C RS, and USP Ketorolac Related Compound D RS in Standard solution from System suitability stock solution

Sample stock solution: 0.2 mg/mL of ketorolac tromethamine prepared as follows. Transfer 10 Tablets to a suitable volumetric flask. Add a quantity of water equivalent to about 10% of the volume of the flask, and sonicate until the Tablets are disintegrated. Add a quantity of methanol equivalent to 40% of the volume of the flask, and sonicate for 10 min to dissolve the ketorolac tromethamine. Cool to ambient temperature, dilute with methanol to volume, and mix. Centrifuge, or allow to settle.

Sample solution: 0.02 mg/mL of ketorolac tromethamine in Diluent from Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector

Assay: UV 254 nm

Identification test B: Diode array, UV 200–400 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.2 mL/min

Injection volume: 100 μL

Run time: 3.8 times the retention time of the ketorolac peak

System suitability

Samples: Standard solution and System suitability solution

[Note—The relative retention times are 0.8 for ketorolac related compound B and 1.0 for the ketorolac peaks.]

Suitability requirements

Resolution: NLT 1.5 each between the ketorolac and ketorolac related compound B, and ketorolac and ketorolac related compound C peaks, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ketorolac tromethamine (C₁₅H₁₃NO₃· C₄H₁₁NO₃ ) in the portion of Tablets taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = response of the ketorolac peak from the Sample solution

r_S = response of the ketorolac peak from the Standard solution

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

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

Acceptance criteria: 90.0%–110%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 600 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: USP Ketorolac Tromethamine RS in Medium

Sample solutions: Sample per Dissolution 〈711〉. Dilute with Medium to a concentration that is similar to the Standard solution.

Instrumental conditions

Mode: UV absorption spectroscopy

Analytical wavelength: 322 nm

Tolerances: NLT 75% (Q) of the labeled amount of ketorolac tromethamine (C₁₅H₁₃NO₃· C₄H₁₁NO₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Mobile phase, Chromatographic system, and Diluent: Proceed as directed in the Assay.

Standard solution: Use the System suitability solution, prepared as directed in the Assay.

Sample solution: Proceed as directed for the Sample solution in the Assay.

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.5 each between the ketorolac and ketorolac related compound B, and ketorolac and ketorolac related compound C peaks

Relative standard deviation: NMT 5.0% for ketorolac related compound A, ketorolac related compound B, ketorolac related compound C, and ketorolac related compound D

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each known impurity in the portion of Tablets taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of each known impurity in the Sample solution

r_S = peak response of each known impurity in the Standard solution

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

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

Calculate the percentage of any other impurity in the portion of Tablets taken:

Result = (r_U /r_T) × 100

r_U = response of each individual impurity peak in the Sample solution

r_T = sum of responses for all the peaks in the Sample solution

Acceptance criteria: See Table 1.

Table 1

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers at controlled room temperature, protected from light and excessive humidity.

USP Reference Standards 〈11〉

USP Ketorolac Tromethamine RS

USP Ketorolac Related Compound A RS

5-Benzoyl-N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]-2,3-dihydro-1H-pyrrolizine-1-carboxamide.

C₁₉H₂₂N₂O₅  358.39

USP Ketorolac Related Compound B RS

5-Benzoyl-2,3-dihydro-1H-pyrrolizin-1-ol.

C₁₄H₁₃NO₂ 227.26

USP Ketorolac Related Compound C RS

5-Benzoyl-2,3-dihydro-1H-pyrrolizin-1-one.

C₁₄H₁₁NO₂ 225.24

USP Ketorolac Related Compound D RS

5-Benzoyl-2,3-dihydro-1H-pyrrolizine.

C₁₄H₁₃NO 211.26