Ketorolac Tromethamine Injection

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 Injection is a sterile solution of Ketorolac Tromethamine. It contains 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 spectrum of the ketorolac peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

[Note—Protect all solutions from light.]

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

Diluent: Methanol and water (1:1)

Standard solution: 0.05 mg/mL of USP Ketorolac Tromethamine RS in Diluent

Sample solution: Nominally equivalent to 0.05 mg/mL of ketorolac tromethamine in Diluent from Injection

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification test B, use a diode array detector in the range of 200–600 nm.

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

Flow rate: 1.2 mL/min

Injection volume: 100 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5 for the ketorolac peak

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ketorolac tromethamine (C₁₅H₁₃NO₃· C₄H₁₁NO₃ ) in each mL of Injection taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of ketorolac from the Sample solution

r_S = peak response of ketorolac 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%–110.0%

4 IMPURITIES

Organic Impurities

[Note—Protect all solutions from light.]

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

Standard stock solution: 0.10 mg/mL each of USP Ketorolac Tromethamine RS, 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 Diluent prepared as follows. Transfer USP Ketorolac Tromethamine RS, 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 to a suitable volumetric flask. Add 4% of the volume of the flask with methanol. Sonicate and dilute with Diluent to volume.

Standard solution: 0.2 μg/mL each of USP Ketorolac Tromethamine RS, 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 Diluent from the Standard stock solution

Sample solution: Prepare nominally equivalent to 0.2 mg/mL of ketorolac tromethamine in Diluent.

System suitability

Sample: Standard solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 2 between ketorolac related compound C and ketorolac

Relative standard deviation: NMT 2.8% for all the peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of ketorolac related compound A, ketorolac related compound B, ketorolac related

compound C, and ketorolac related compound D in the portion of Injection taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of ketorolac related compound A, ketorolac related compound B, ketorolac related compound C, or ketorolac related compound D from the Sample solution

r_S = peak response of ketorolac related compound A, ketorolac related compound B, ketorolac related compound C, or ketorolac related compound D from the Standard solution

C_S = concentration of the corresponding related compound in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Injection taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of any unspecified impurity from the Sample solution

r_S = peak response of ketorolac 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: See Table 1. Disregard any impurity peak less than 0.05%.

Table 1

5 SPECIFIC TESTS

pH 〈791〉: 6.9–7.9

Bacterial Endotoxins Test 〈85〉: It contains NMT 5.8 USP Endotoxin Units/mg of ketorolac tromethamine.

Sterility Tests 〈71〉: Meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined, Membrane Filtration

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose containers, preferably of Type I glass, protected from light, and store at controlled room temperature.

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 211.3