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Ketorolac Tromethamine Injection
» Ketorolac Tromethamine Injection is a sterile solution of Ketorolac Tromethamine. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of ketorolac tromethamine (C15H13NO3·C4H11NO3).
Packaging and storage— Preserve in single-dose containers, preferably of Type I glass, at controlled room temperature, protected from light.
Identification— Prepare a mixture of the Standard preparation and the Assay preparation (1:1), and chromatograph the mixture as directed in the Assay. The chromatogram thus obtained exhibits two main peaks corresponding to ketorolac and the internal standard.
Bacterial endotoxins 85 It contains not more than 5.8 USP Endotoxin Units per mg of ketorolac tromethamine.
Sterility 71 It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
pH 791: between 6.9 and 7.9.
Particulate matter 788: meets the requirements for small-volume injections.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Other requirements— It meets the requirements under Injections 1.
Mobile phase— Prepare a filtered and degassed mixture of methanol, water, and glacial acetic acid (55:44:1). Make adjustments if necessary (see System Suitability under Chromatography 621). Resolution may be increased by increasing the proportion of water in the Mobile phase.
Solvent mixture— Prepare a mixture of methanol and water (1:1).
Internal standard solution— Prepare a solution of naproxen in methanol containing about 0.3 mg per mL.
Standard stock solution— Dissolve an accurately weighed quantity of USP Ketorolac Tromethamine RS quantitatively in methanol to obtain a solution having a known concentration of about 0.24 mg per mL. [NOTE—Protect this solution from light.]
Standard preparation— Transfer 5.0 mL of the Standard stock solution and 5.0 mL of the Internal standard solution to a 50-mL volumetric flask, dilute with Solvent mixture to volume, and mix. [NOTE—Protect this solution from light.]
Assay preparation— Transfer an accurately measured volume of the Injection, equivalent to about 12 mg of ketorolac tromethamine, to a 50-mL volumetric flask, dilute with methanol to volume, and mix. Transfer 5.0 mL of this stock solution and 5.0 mL of Internal standard solution to a second 50-mL volumetric flask, dilute with Solvent mixture to volume, and mix. [NOTE—Protect both the stock solution and the Assay preparation from light.]
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for ketorolac and 1.0 for naproxen, the resolution, R, between the ketorolac peak and the naproxen peak is not less than 5.4, the column efficiency determined from the ketorolac peak is not less than 2700 theoretical plates, the tailing factor is not more than 1.5, and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure— Separately inject equal volumes (about 100 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of ketorolac tromethamine (C15H13NO3·C4H11NO3) in each mL of the Injection taken by the formula:
50(C / V)(RU / RS),
in which C is the concentration, in mg per mL, of USP Ketorolac Tromethamine RS in the Standard stock solution; V is the volume, in mL, of Injection taken to prepare the Assay preparation; and RU and RS are the ratios of the ketorolac peak response to the naproxen peak response obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Clydewyn M. Anthony, Ph.D., Scientist
Expert Committee : (MDCCA05) Monograph Development-Cough Cold and Analgesics
USP29–NF24 Page 1219
Phone Number : 1-301-816-8139